Information

18.4: B Lymphocytes and Antibodies - Biology


Learning Objectives

  • Describe the production and maturation of B cells
  • Compare the structure of B-cell receptors and T-cell receptors
  • Compare T-dependent and T-independent activation of B cells
  • Compare the primary and secondary antibody responses

Humoral immunity refers to mechanisms of the adaptive immune defenses that are mediated by antibodies secreted by B lymphocytes, or B cells. This section will focus on B cells and discuss their production and maturation, receptors, and mechanisms of activation.

B Cell Production and Maturation

Like T cells, B cells are formed from multipotent hematopoietic stem cells (HSCs) in the bone marrow and follow a pathway through lymphoid stem cell and lymphoblast (see [link]). Unlike T cells, however, lymphoblasts destined to become B cells do not leave the bone marrow and travel to the thymus for maturation. Rather, eventual B cells continue to mature in the bone marrow.

The first step of B cell maturation is an assessment of the functionality of their antigen-binding receptors. This occurs through positive selection for B cells with normal functional receptors. A mechanism of negative selection is then used to eliminate self-reacting B cells and minimize the risk of autoimmunity. Negative selection of self-reacting B cells can involve elimination by apoptosis, editing or modification of the receptors so they are no longer self-reactive, or induction of anergy in the B cell. Immature B cells that pass the selection in the bone marrow then travel to the spleenfor their final stages of maturation. There they become naïve mature B cells, i.e., mature B cells that have not yet been activated.

Exercise (PageIndex{1})

Compare the maturation of B cells with the maturation of T cells.

B-Cell Receptors

Like T cells, B cells possess antigen-specific receptors with diverse specificities. Although they rely on T cells for optimum function, B cells can be activated without help from T cells. B-cell receptors (BCRs) for naïve mature B cells are membrane-bound monomeric forms of IgD and IgM. They have two identical heavy chains and two identical light chains connected by disulfide bonds into a basic “Y” shape (Figure (PageIndex{1})). The trunk of the Y-shaped molecule, the constant region of the two heavy chains, spans the B cell membrane. The two antigen-binding sites exposed to the exterior of the B cell are involved in the binding of specific pathogen epitopes to initiate the activation process. It is estimated that each naïve mature B cell has upwards of 100,000 BCRs on its membrane, and each of these BCRs has an identical epitope-binding specificity.

In order to be prepared to react to a wide range of microbial epitopes, B cells, like T cells, use genetic rearrangementof hundreds of gene segments to provide the necessary diversity of receptor specificities. The variable region of the BCR heavy chain is made up of V, D, and J segments, similar to the β chain of the TCR. The variable region of the BCR light chain is made up of V and J segments, similar to the α chain of the TCR. Genetic rearrangement of all possible combinations of V-J-D (heavy chain) and V-J (light chain) provides for millions of unique antigen-binding sites for the BCR and for the antibodies secreted after activation.

One important difference between BCRs and TCRs is the way they can interact with antigenic epitopes. Whereas TCRs can only interact with antigenic epitopes that are presented within the antigen-binding cleft of MHC I or MHC II, BCRs do not require antigen presentation with MHC; they can interact with epitopes on free antigens or with epitopesdisplayed on the surface of intact pathogens. Another important difference is that TCRs only recognize protein epitopes, whereas BCRs can recognize epitopes associated with different molecular classes (e.g., proteins, polysaccharides, lipopolysaccharides).

Activation of B cells occurs through different mechanisms depending on the molecular class of the antigen. Activation of a B cell by a protein antigen requires the B cell to function as an APC, presenting the protein epitopes with MHC II to helper T cells. Because of their dependence on T cells for activation of B cells, protein antigens are classified as T-dependent antigens. In contrast, polysaccharides, lipopolysaccharides, and other nonprotein antigens are considered T-independent antigens because they can activate B cells without antigen processing and presentation to T cells.

Exercise (PageIndex{2})

  1. What types of molecules serve as the BCR?
  2. What are the differences between TCRs and BCRs with respect to antigen recognition?
  3. Which molecule classes are T-dependent antigens and which are T-independent antigens?

T Cell-Independent Activation of B cells

Activation of B cells without the cooperation of helper T cells is referred to as T cell-independent activation and occurs when BCRs interact with T-independent antigens. T-independent antigens (e.g., polysaccharide capsules, lipopolysaccharide) have repetitive epitope units within their structure, and this repetition allows for the cross-linkageof multiple BCRs, providing the first signal for activation (Figure (PageIndex{2})). Because T cells are not involved, the second signal has to come from other sources, such as interactions of toll-like receptors with PAMPs or interactions with factors from the complement system.

Once a B cell is activated, it undergoes clonal proliferation and daughter cells differentiate into plasma cells. Plasma cells are antibody factories that secrete large quantities of antibodies. After differentiation, the surface BCRs disappear and the plasma cell secretes pentameric IgM molecules that have the same antigen specificity as the BCRs (Figure (PageIndex{2})).

The T cell-independent response is short-lived and does not result in the production of memory B cells. Thus it will not result in a secondary response to subsequent exposures to T-independent antigens.

Exercise (PageIndex{3})

  1. What are the two signals required for T cell-independent activation of B cells?
  2. What is the function of a plasma cell?

T Cell-Dependent Activation of B cells

T cell-dependent activation of B cells is more complex than T cell-independent activation, but the resulting immune response is stronger and develops memory. T cell-dependent activation can occur either in response to free protein antigens or to protein antigens associated with an intact pathogen. Interaction between the BCRs on a naïve mature B cell and a free protein antigen stimulate internalization of the antigen, whereas interaction with antigens associated with an intact pathogen initiates the extraction of the antigen from the pathogen before internalization. Once internalized inside the B cell, the protein antigen is processed and presented with MHC II. The presented antigen is then recognized by helper T cells specific to the same antigen. The TCR of the helper T cell recognizes the foreign antigen, and the T cell’s CD4 molecule interacts with MHC II on the B cell. The coordination between B cells and helper T cells that are specific to the same antigen is referred to as linked recognition.

Once activated by linked recognition, TH2 cells produce and secrete cytokines that activate the B cell and cause proliferation into clonal daughter cells. After several rounds of proliferation, additional cytokines provided by the TH2 cells stimulate the differentiation of activated B cell clones into memory B cells, which will quickly respond to subsequent exposures to the same protein epitope, and plasma cells that lose their membrane BCRs and initially secrete pentameric IgM (Figure (PageIndex{3})).

After initial secretion of IgM, cytokines secreted by TH2 cells stimulate the plasma cells to switch from IgM production to production of IgG, IgA, or IgE. This process, called class switching or isotype switching, allows plasma cellscloned from the same activated B cell to produce a variety of antibody classes with the same epitope specificity. Class switching is accomplished by genetic rearrangement of gene segments encoding the constant region, which determines an antibody’s class. The variable region is not changed, so the new class of antibody retains the original epitope specificity.

Exercise (PageIndex{4})

  1. What steps are required for T cell-dependent activation of B cells?
  2. What is antibody class switching and why is it important?

Primary and Secondary Responses

T cell-dependent activation of B cells plays an important role in both the primary and secondary responses associated with adaptive immunity. With the first exposure to a protein antigen, a T cell-dependent primary antibody responseoccurs. The initial stage of the primary response is a lag period, or latent period, of approximately 10 days, during which no antibody can be detected in serum. This lag period is the time required for all of the steps of the primary response, including naïve mature B cell binding of antigen with BCRs, antigen processing and presentation, helper T cell activation, B cell activation, and clonal proliferation. The end of the lag period is characterized by a rise in IgM levels in the serum, as TH2 cells stimulate B cell differentiation into plasma cells. IgM levels reach their peak around 14 days after primary antigen exposure; at about this same time, TH2 stimulates antibody class switching, and IgM levels in serum begin to decline. Meanwhile, levels of IgG increase until they reach a peak about three weeks into the primary response (Figure (PageIndex{4})).

During the primary response, some of the cloned B cells are differentiated into memory B cells programmed to respond to subsequent exposures. This secondary response occurs more quickly and forcefully than the primary response. The lag period is decreased to only a few days and the production of IgG is significantly higher than observed for the primary response (Figure (PageIndex{4})). In addition, the antibodies produced during the secondary response are more effective and bind with higher affinity to the targeted epitopes. Plasma cells produced during secondary responses live longer than those produced during the primary response, so levels of specific antibody remain elevated for a longer period of time.

Exercise (PageIndex{5})

  1. What events occur during the lag period of the primary antibody response?
  2. Why do antibody levels remain elevated longer during the secondary antibody response?

Key Concepts and Summary

  • B lymphocytes or B cells produce antibodies involved in humoral immunity. B cells are produced in the bone marrow, where the initial stages of maturation occur, and travel to the spleen for final steps of maturation into naïve mature B cells.
  • B-cell receptors (BCRs) are membrane-bound monomeric forms of IgD and IgM that bind specific antigen epitopes with their Fab antigen-binding regions. Diversity of antigen binding specificity is created by genetic rearrangement of V, D, and J segments similar to the mechanism used for TCR diversity.
  • Protein antigens are called T-dependent antigens because they can only activate B cells with the cooperation of helper T cells. Other molecule classes do not require T cell cooperation and are called T-independent antigens.
  • T cell-independent activation of B cells involves cross-linkage of BCRs by repetitive nonprotein antigen epitopes. It is characterized by the production of IgM by plasma cells and does not produce memory B cells.
  • T cell-dependent activation of B cells involves processing and presentation of protein antigens to helper T cells, activation of the B cells by cytokines secreted from activated TH2 cells, and plasma cells that produce different classes of antibodies as a result of class switching. Memory B cells are also produced.
  • Secondary exposures to T-dependent antigens result in a secondary antibody response initiated by memory B cells. The secondary response develops more quickly and produces higher and more sustained levels of antibody with higher affinity for the specific antigen.

Multiple Choice

Which of the following would be a T-dependent antigen?

A. lipopolysaccharide
B. glycolipid
C. protein
D. carbohydrate

C

Which of the following would be a BCR?

A. CD4
B. MHC II
C. MHC I
D. IgD

D

Which of the following does not occur during the lag period of the primary antibody response?

A. activation of helper T cells
B. class switching to IgG
C. presentation of antigen with MHC II
D. binding of antigen to BCRs

B

Fill in the Blank

________ antigens can stimulate B cells to become activated but require cytokine assistance delivered by helper T cells.

T-dependent

T-independent antigens can stimulate B cells to become activated and secrete antibodies without assistance from helper T cells. These antigens possess ________ antigenic epitopes that cross-link BCRs.

repetitive

Critical Thinking

A patient lacks the ability to make functioning T cells because of a genetic disorder. Would this patient’s B cells be able to produce antibodies in response to an infection? Explain your answer.


How Antibodies Defend Your Body

Antibodies (also called immunoglobulins) are specialized proteins that travel through the bloodstream and are found in bodily fluids. They are used by the immune system to identify and defend against foreign intruders to the body.

These foreign intruders, or antigens, include any substance or organism that evokes an immune response.

Examples of antigens that cause immune responses include

Antibodies recognize specific antigens by identifying certain areas on the surface of the antigen known as antigenic determinants. Once the specific antigenic determinant is recognized, the antibody will bind to the determinant. The antigen is tagged as an intruder and labeled for destruction by other immune cells. Antibodies protect against substances prior to cell infection.


B Cell Differentiation and Activation

B cells differentiate in the bone marrow. During the process of maturation, up to 100 trillion different clones of B cells are generated, which is similar to the diversity of antigen receptors seen in T cells.

After B cells are activated by their binding to antigen, they differentiate into plasma cells. Plasma cells often leave the secondary lymphoid organs, where the response is generated, and migrate back to the bone marrow, where the whole differentiation process started. After secreting antibodies for a specific period, they die, as most of their energy is devoted to making antibodies and not to maintaining themselves. Thus, plasma cells are said to be terminally differentiated.

Memory B cells function in a way similar to memory T cells. They lead to a stronger and faster secondary response when compared to the primary response, as illustrated below.


What Is the Relationship between Lymphocytes and Antibodies?

A lymphocyte is a type of white blood cell which helps to recognize and fight infection as part of the immune system. Also in the immune system are proteins called antibodies, which attach to harmful substances such as microbes and help destroy them. Lymphocytes can be divided into two main groups, known as T cells and B cells. An important relationship between B lymphocytes and antibodies exists, because B cells are able to develop into what are called plasma cells. Plasma cells are responsible for releasing antibodies into the circulation.

Lymphocytes and antibodies are vital parts of the human immune response. B and T cells work together to recognize and dispose of antigens such as bacteria and viruses. Antibody production is an essential part of the process and, without antibodies, humans would soon die from infections. Inside the immune system, both B and T cells recognize their own specific antigens, which attach to receptors on their cell surfaces. Some T cells then activate B cells, while others kill infected cells.

There are many different B and T lymphocytes and antibodies, able to respond to every antigen which might invade the body. When a B cell has been activated by a T cell, it divides and develops into antibody-secreting plasma cells and memory cells which remember antigens. Initially, the antibodies made by a developing B cell are not released but attach to the cell surface, forming antigen receptors. Then, the B cell matures into a plasma cell that can secrete thousands of antibodies every second. All of the antibodies produced by a plasma cell will bind to the same type of antigen that originally triggered their production.

When antibodies bind to their specific antigens they neutralize them, or make them attractive to other immune cells which consume and destroy them. A further connection between lymphocytes and antibodies is seen when antigens bind to those B cell receptors which were formed from the first antibodies to be produced. This binding helps activate more B cells, stimulating them to develop into antibody-secreting cells and memory cells.

The structures of lymphocytes and antibodies are quite different. In most cases, a lymphocyte such as a B cell or T cell is what is known as an agranular cell, where the gel, or cytoplasm, that fills the cell is clear. The only granular lymphocytes are called natural killer cells, and these differ from B and T cells in that they are not specific and can recognize different kinds of antigens. Antibodies are not cells. They are typically Y-shaped proteins, with antigen-binding sites on the arms of the Y and cell receptor binding sites on its tail.


Understanding How Vaccines Work

To understand how vaccines work, it helps to first look at how the body fights illness. When germs, such as bacteria or viruses, invade the body, they attack and multiply. This invasion, called an infection, is what causes illness. The immune system uses several tools to fight infection. Blood contains red blood cells, for carrying oxygen to tissues and organs, and white or immune cells, for fighting infection. These white cells consist primarily of macrophages, B-lymphocytes and T-lymphocytes:

Vaccines prevent diseases that can be dangerous, or even deadly. Vaccines greatly reduce the risk of infection by working with the body&rsquos natural defenses to safely develop immunity to disease. This fact sheet explains how the body fights infection and how vaccines work to protect people by producing immunity.

  • Macrophages media icon are white blood cells that swallow up and digest germs, plus dead or dying cells. The macrophages leave behind parts of the invading germs called antigens. The body identifies antigens as dangerous and stimulates antibodies to attack them.
  • B-lymphocytes are defensive white blood cells. They produce antibodies that attack the antigens left behind by the macrophages.
  • T-lymphocytes are another type of defensive white blood cell. They attack cells in the body that have already been infected.

The first time the body encounters a germ, it can take several days to make and use all the germ-fighting tools needed to get over the infection. After the infection, the immune system remembers what it learned about how to protect the body against that disease.

The body keeps a few T-lymphocytes, called memory cells, that go into action quickly if the body encounters the same germ again. When the familiar antigens are detected, B-lymphocytes produce antibodies to attack them.

How Vaccines Work

Vaccines help develop immunity by imitating an infection. This type of infection, however, almost never causes illness, but it does cause the immune system to produce T-lymphocytes and antibodies. Sometimes, after getting a vaccine, the imitation infection can cause minor symptoms, such as fever. Such minor symptoms are normal and should be expected as the body builds immunity.

Once the imitation infection goes away, the body is left with a supply of &ldquomemory&rdquo T-lymphocytes, as well as B-lymphocytes that will remember how to fight that disease in the future. However, it typically takes a few weeks for the body to produce T-lymphocytes and B-lymphocytes after vaccination. Therefore, it is possible that a person infected with a disease just before or just after vaccination could develop symptoms and get a disease, because the vaccine has not had enough time to provide protection.

Types of Vaccines

Scientists take many approaches to developing vaccines. These approaches are based on information about the infections (caused by viruses or bacteria) the vaccine will prevent, such as how germs infect cells and how the immune system responds to it. Practical considerations, such as regions of the world where the vaccine would be used, are also important because the strain of a virus and environmental conditions, such as temperature and risk of exposure, may be different across the globe. The vaccine delivery options available may also differ geographically. Today there are five main types of vaccines that infants and young children commonly receive in the U.S.:

  • Live, attenuated vaccines fight viruses and bacteria. These vaccines contain a version of the living virus or bacteria that has been weakened so that it does not cause serious disease in people with healthy immune systems. Because live, attenuated vaccines are the closest thing to a natural infection, they are good teachers for the immune system. Examples of live, attenuated vaccines include measles, mumps, and rubella vaccine (MMR) and varicella (chickenpox) vaccine. Even though they are very effective, not everyone can receive these vaccines. Children with weakened immune systems&mdashfor example, those who are undergoing chemotherapy&mdashcannot get live vaccines.
  • Inactivated vaccines also fight viruses and bacteria. These vaccines are made by inactivating, or killing, the germ during the process of making the vaccine. The inactivated polio vaccine is an example of this type of vaccine. Inactivated vaccines produce immune responses in different ways than live, attenuated vaccines. Often, multiple doses are necessary to build up and/or maintain immunity.
  • Toxoid vaccines prevent diseases caused by bacteria that produce toxins (poisons) in the body. In the process of making these vaccines, the toxins are weakened so they cannot cause illness. Weakened toxins are called toxoids. When the immune system receives a vaccine containing a toxoid, it learns how to fight off the natural toxin. The DTaP vaccine contains diphtheria and tetanus toxoids.
  • Subunit vaccines include only parts of the virus or bacteria, or subunits, instead of the entire germ. Because these vaccines contain only the essential antigens and not all the other molecules that make up the germ, side effects are less common. The pertussis (whooping cough) component of the DTaP vaccine is an example of a subunit vaccine.
  • Conjugate vaccines fight a different type of bacteria. These bacteria have antigens with an outer coating of sugar-like substances called polysaccharides. This type of coating disguises the antigen, making it hard for a young child&rsquos immature immune system to recognize it and respond to it. Conjugate vaccines are effective for these types of bacteria because they connect (or conjugate) the polysaccharides to antigens that the immune system responds to very well. This linkage helps the immature immune system react to the coating and develop an immune response. An example of this type of vaccine is the Haemophilus influenzae type B (Hib) vaccine.

Vaccines Require More Than One Dose

There are four reasons that babies&mdashand even teens or adults&mdashwho receive a vaccine for the first time may need more than one dose:

  • For some vaccines (primarily inactivated vaccines), the first dose does not provide as much immunity as possible. So, more than one dose is needed to build more complete immunity. The vaccine that protects against the bacteria Hib, which causes meningitis, is a good example.
  • For some vaccines, after a while, immunity begins to wear off. At that point, a &ldquobooster&rdquo dose is needed to bring immunity levels back up. This booster dose usually occurs several years after the initial series of vaccine doses is given. For example, in the case of the DTaP vaccine, which protects against diphtheria, tetanus and pertussis, the initial series of four shots that children receive as part of their infant immunizations helps build immunity. But a booster dose is needed at 4 years through 6 years old. Another booster against these diseases is needed at 11 years or 12 years of age. This booster for older children&mdashand teens and adults, too&mdashis called Tdap.
  • For some vaccines (primarily live vaccines), studies have shown that more than one dose is needed for everyone to develop the best immune response. For example, after one dose of the MMR vaccine, some people may not develop enough antibodies to fight off infection. The second dose helps make sure that almost everyone is protected.
  • Finally, in the case of flu vaccines, adults and children (6 months and older) need to get a dose every year. Children 6 months through 8 years old who have never gotten a flu vaccine in the past or have only gotten one dose in past years need two doses the first year they are vaccinated. Then, an annual flu vaccine is needed because the flu viruses causing disease may be different from season to season. Every year, flu vaccines are made to protect against the viruses that research suggests will be most common. Also, the immunity a child gets from a flu vaccination wears off over time. Getting a flu vaccine every year helps keep a child protected, even if the vaccine viruses don&rsquot change from one season to the next.

The Bottom Line

Some people believe that naturally acquired immunity&mdashimmunity from having the disease itself&mdashis better than the immunity provided by vaccines. However, natural infections can cause severe complications and be deadly. This is true even for diseases that many people consider mild, like chickenpox. It is impossible to predict who will get serious infections that may lead to hospitalization.


Immune Response

Pathogens are organisms which cause disease. We’re all adapted to prevent these from getting into our bodies in the first place. If a pathogen does manage to sneak it’s way in, our immune system kicks into action, activating various types of white blood cells to manufacture antibodies and kill the pathogen.

Barriers to prevent entry of pathogens

Our bodies have several defensive barriers to prevent us becoming infected by pathogens. For example:

Our body cavities (e.g. eyes, nose, mouth, genitals) are lined with a mucus membrane which contain an enzyme called lysozyme. Lysozyme kills bacteria by damaging their cell walls, causing them to burst open.

Our skin acts as a physical barrier to stop pathogens from getting inside of us. If our skin is cut or wounded, our blood quickly clots to minimise the entry of pathogens.

The trachea (windpipe) contains goblet cells which secrete mucus. Pathogens that we inhale become trapped in the mucus, which is swept towards the stomach by the action of ciliated epithelial cells.

Our stomach contains gastric juices which are highly acidic - these will denature proteins and kill any pathogens that have been ingested in our food and drinks.

The insides of our intestines and the surface of our skin are covered in harmless bacteria which will compete with any pathogenic organisms and reduce their ability to grow.

Barriers against the entry of pathogens into the body.

Non-Specific Immune Response

The non-specific immune response is our immediate response to infection and is carried out in exactly the same way regardless of the pathogen (i.e. it is not specific to a particular pathogen). The non-specific immune response involves inflammation, the production of interferons and phagocytosis.

Inflammation - the proteins which are found on the surface of a pathogen (antigens) are detected by our immune system. Immune cells release molecules to stimulate vasodilation (the widening of blood vessels) and to make the blood vessels more permeable. This means that more immune cells can arrive at the site of infection by moving out of the bloodstream and into the infected tissue. The increased blood flow is why an inflamed part of your body looks red and swollen.

Production of interferons - if the pathogen which has infected you is a virus, your body cells that have been invaded by the virus will start to manufacture anti-viral proteins called interferons. They slow down viral replication in three different ways:

Stimulate inflammation to bring more immune cells to the site of infection

Inhibit the translation of viral proteins to reduce viral replication

Activate T killer cells to destroy infected cells

Phagocytosis

Phagocytes are a type of white blood cell which can destroy pathogens - types of phagocyte include macrophages, monocytes and neutrophils. They first detect the presence of the pathogen when receptors on its cell surface bind to antigens on the pathogen. The phagocyte then wraps its cytoplasm around the pathogen and engulfs it. The pathogen is contained within a type of vesicle called a phagosome. Another type of vesicle, called a lysosome, which contains digestive enzymes (lysozymes) will fuse with the phagosome to form a phagolysosome. Lysozymes digest the pathogen and destroy it. The digested pathogen will be removed from the phagocyte by exocytosis but they will keep some antigen molecules to present on the surface of their cells - this serves to alert other cells of the immune system to the presence of a foreign antigen. The phagocyte is now referred to as an antigen-presenting cell (APC).


Defence Mechanisms

  • Natural Barriers – Skins, Mucous Linings and Blood Clotting.
  • The human body is an ideal incubator for micro organisms. Many live in or on our bodies (commensals) causing no harm and benefiting. Pathogens are disease causing micro organisms and enter in two ways, either through the skin or natural openings.
  • The skin is an effective barrier due to its thin continuous keratinised layer.
  • Micro organisms can be washed off easily and skin can flake off which helps to prevent a build up of bacteria.
  • Lysozyme in the eyes breaks down bacterial cell walls.
  • Invasion only occurs when skin is broken.

Antigens

An antigen is any substance that when introduced into the blood or tissue induces the production of antibodies. Most cells possess antigens in their cell surface membrane which act as markers enabling cells to recognise each other.

Antigens are usually large complex molecules such as proteins or glycoproteins, although any complex can be antigenic. The body can then distinguish between local and foreign cells but only usually make antibodies in response to foreign antigens.

Antibodies

An antibody is a protein produced by lymphocytes in the presence of a specific, usually foreign, antigen. As seen from the diagram above, antibodies are Y-shaped and are made up from polypeptide chains. When an antibody encounters a foreign antigen it can then join with the specific antigen and neutralise, inhibit or destroy it.


Helper T Lymphocytes

The TH lymphocytes function indirectly to identify potential pathogens for other cells of the immune system. These cells are important for extracellular infections, such as those caused by certain bacteria, helminths, and protozoa. TH lymphocytes recognize specific antigens displayed in the MHC II complexes of APCs. There are two major populations of TH cells: TH1 and TH2. TH1 cells secrete cytokines to enhance the activities of macrophages and other T cells. TH1 cells activate the action of cyotoxic T cells, as well as macrophages. TH2 cells stimulate naïve B cells to destroy foreign invaders via antibody secretion. Whether a TH1 or a TH2 immune response develops depends on the specific types of cytokines secreted by cells of the innate immune system, which in turn depends on the nature of the invading pathogen.

The TH1-mediated response involves macrophages and is associated with inflammation. Recall the frontline defenses of macrophages involved in the innate immune response. Some intracellular bacteria, such as Mycobacterium tuberculosis, have evolved to multiply in macrophages after they have been engulfed. These pathogens evade attempts by macrophages to destroy and digest the pathogen. When M. tuberculosis infection occurs, macrophages can stimulate naïve T cells to become TH1 cells. These stimulated T cells secrete specific cytokines that send feedback to the macrophage to stimulate its digestive capabilities and allow it to destroy the colonizing M. tuberculosis. In the same manner, TH1-activated macrophages also become better suited to ingest and kill tumor cells. In summary TH1 responses are directed toward intracellular invaders while TH2 responses are aimed at those that are extracellular.


Molecular Biology of B Cells

Molecular Biology of B Cells, Second Edition is a comprehensive reference to how B cells are generated, selected, activated and engaged in antibody production. All of these developmental and stimulatory processes are described in molecular, immunological, and genetic terms to give a clear understanding of complex phenotypes.

Molecular Biology of B Cells, Second Edition offers an integrated view of all aspects of B cells to produce a normal immune response as a constant, and the molecular basis of numerous diseases due to B cell abnormality. The new edition continues its success with updated research on microRNAs in B cell development and immunity, new developments in understanding lymphoma biology, and therapeutic targeting of B cells for clinical application. With updated research and continued comprehensive coverage of all aspects of B cell biology, Molecular Biology of B Cells, Second Edition is the definitive resource, vital for researchers across molecular biology, immunology and genetics.

Molecular Biology of B Cells, Second Edition is a comprehensive reference to how B cells are generated, selected, activated and engaged in antibody production. All of these developmental and stimulatory processes are described in molecular, immunological, and genetic terms to give a clear understanding of complex phenotypes.

Molecular Biology of B Cells, Second Edition offers an integrated view of all aspects of B cells to produce a normal immune response as a constant, and the molecular basis of numerous diseases due to B cell abnormality. The new edition continues its success with updated research on microRNAs in B cell development and immunity, new developments in understanding lymphoma biology, and therapeutic targeting of B cells for clinical application. With updated research and continued comprehensive coverage of all aspects of B cell biology, Molecular Biology of B Cells, Second Edition is the definitive resource, vital for researchers across molecular biology, immunology and genetics.


Definition of Autoimmune Disease

Autoimmune diseases develop when the auto-reactive B lymphocytes (autoantibodies) and T lymphocytes described above cause a pathological and/or functional damage to the organ/tissue containing the target autoantigen(s). Thus, in autoimmune diseases the auto-reactive lymphocytes are the actual cause of the disease, rather than a harmless accompaniment.

In autoimmune diseases, auto-reactive lymphocytes expand polyclonally because the mechanisms that normally keep them at bay fail. In other words, autoimmune diseases can be considered a manifestation of immune dysregulation.

The term “polyclonal” in this context is used to indicate that in an autoimmune disease there are many different types of autoreactive lymphocytes (rather than multiple copies of the same lymphocyte). These lymphocytes that expand have different antigen receptors on their surface, recognizing different targets (called epitopes) within a single protein or a group of proteins. The term polyclonal distinguishes the expansion of lymphocytes seen in autoimmunity from that seen in malignancies where the expanded lymphocytes are all monoclonal (that is, identical copies of each other).

It is the expansion of these auto-reactive lymphocytes that ultimately causes pathological damage and hence the clinical disease. Damage occurs by a variety of mechanisms (discussed in the Type of Damage section).

Affinity maturation: the process through which B cells mature and produce antibodies that have a greater affinity for their antigenic target. This process is more prominent when the immune response is well under way.

A receptor expressed on the surface of muscle cells at the junction between muscles and nerves. The receptor binds acetylcholine, a molecule released by the nerves that induces muscle contraction.

Enzymes that transfer phosphate groups from a donor (such as ATP) to proteins. Tyrosine kinase can become the target of an autoimmune response.

An autoimmune disease observed in infants caused by the passage of autoantibodies against Ro and/or La antigens from the mother to the baby. The disease can be very severe because these antibodies are capable of causing heart block.

An autoimmune disease caused by the presence of autoantibodies directed against desmoglein 1, a protein part of of the desmosome. Desmosomes are structures that keep cells of the skin tightly together. Antibodies disrupt this connection, resulting in the formation of blisters.

An autoimmune disease caused by the presence of autoantibodies directed against desmoglein 3, a protein part of the desmosome. Desmosomes are structures that keep cells of the skin tightly together. Antibodies disrupt this connection, resulting in the formation of blisters.

An autoimmune disease caused by the presence of autoantibodies directed against the blood platelets, which are necessary for normal blood clotting. Patients have characteristic bleeding manifestations.

An autoimmune disease caused by the presence of autoantibodies directed against the acetylcholine receptor, which is located on skeletal muscle. Patients have characteristic muscle weakness.

Aggregates of immune cells, mainly B cells and T cells, that develop in organs affected by autoimmunity, organs that normally do not contain lymphocytes.

The human leukocytes antigen (HLA) system is the MHC in the human species.

The major histocompatibility complex (MHC) is a cluster of genes that make proteins expressed on the cell-surface that are involved in antigen processing and other immune functions. The MHC genes are the most polymorphic genes we have, meaning that the same gene has slightly different sequences in different people.

The position of a gene on a chromosome. When the same gene has different versions in different people, these versions (called "alleles") still occupy the same locus.

A technique used to quantify proteins (such as antibodies and antigens) based on how they scatter light when put in a solution.

Any virus, bacterium, parasite, or fungus that can enter into the human body and cause disease.

A technique used to determine the presence of antibodies in the patient's serum, revealed by their binding to a purified antigen of interest attached to a plastic plate. After binding to the antigen, the patient antibodies are detected by the addition of a commercially-available antibody directed against human antibodies that has been coupled to an enzyme.

A technique used to determine the presence of antibodies in the patient's serum, revealed by their binding to a purified antigen of interest attached to magnetic beads. After binding to the antigen, the patient antibodies are detected by the addition of a commercial antibody directed against human antibodies that has been coupled to a light-emitting molecule.

A technique used to determine the presence of antibodies in the patient's serum, revealed by their binding to a particular tissue substrate of interest. After binding to the tissue, the patient antibodies are detected by the addition of a commercial antibody directed against human antibodies that has been coupled to a fluorescent dye.

Immune checkpoints are molecules that normally regulate the immune response by putting a brake on T cells. When checkpoints are inhibited, T cells become unleashed and can be used to destroy cancer cells. At the same time, this inhibition of the checkpoints makes T cells more capable of causing autoimmune diseases.

T cells that recognize antigens belonging to the patient (such as thyroglobulin in he thyroid or myosin in the heart), rather than antigens in bacteria and viruses.

Consisting of or derived from many clones.

Several forms of alteration of the immune system where the normal balance between the various immune components is altered.

A disease initiated by infection with some Streptococcus species where the patient makes antibodies against these bacteria that however also recognize with heart antigens, such as cardiac myosin.

The part of the antigen that is recognized by an antibody or a T-cell receptor.

Also known as B cells, these lymphocytes have a surface receptor specific for one of many antigens. B cells also secrete antibodies that when directed against self components are called autoantibodies (as found in patients with autoimmune diseases).

Also known as T cells, these lymphocytes are one of the two lymphocyte types that have antigen-specific receptors on their surface and mediate adaptive immunity (the other type is the B lymphocyte).

Any molecule that can be recognized specifically by antibodies or T lymphocytes. Typically the recognition is focused on some parts of the antigen (rather than the entire antigen), which are called epitopes.

The type of antibodies that recognize antigens of the patient, always present in autoimmune diseases and sometimes causing them.

A normal component of the patient, such as a protein or a protein-nucleic acid complex, that becomes recognized by the patient's own antibodies and/or T lymphocytes during an autoimmune disease.

Proteins produced by B lymphocytes and plasma cells that recognize specific molecules called antigens.

The collection of characteristics of a person (morphological, physiological, biochemical, etc), as determined by his/her genotype and environment.

The hardening of a tissue caused by an abnormal deposition of collagen fibers. For example, sclerosis of the skin in scleroderma and sclerosis of the kidney in diabetic patients who develop glomerular disease.

An autoimmune disease targeting the skin melanocytes and producing characteristic patches of discoloration that are disfiguring and dampen patient's self-esteem and quality of life.

A systemic autoimmune disease affecting the skin (dermatomyositis), the striated muscles (polymyositis), and often other targets (from the joints to the lungs).

An autoimmune disease predominantly targeting the thyroid gland, and mediated by autoantibodies that bind to and stimulate a receptor expressed on thyroid cells called TSH receptor.

A systemic autoimmune disease affecting the joints (with a pattern similar to rheumatoid arthritis) and a variety of other organs (ranging from kidney, heart, muscles, to the nervous system), the skin, and often other organs (such as lungs, and gastro-intestinal system).

A systemic autoimmune disease affecting the joints (with a pattern similar to rheumatoid arthritis) and a variety of other organs (ranging from kidney, heart, muscles, to the nervous system).

A systemic autoimmune disease primarily targeting the membrane (called synovium) that line peripheral joints (such as those of the hand, elbow, shoulder, knee and hip).