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Adaptive Immunity

B Cells

B cell differentiation occurs by random gene rearrangement that results in specificity for different antigens, and B cells rapidly proliferate after encountering their target antigen.

The life cycle of B lymphocyte adaptive immune cells, or B cells, begins in the bone marrow. Hematopoietic stem cells, or cells that have the potential to differentiate into any immune cell type, become B cells by turning on specific genes. In the bone marrow, newly forming B cells progress through several phases: pro-B cells undergo a gene rearrangement process, pre-B cells are the first phase to express a B cell receptor on their cell surface, and immature B cells express a functional antibody on their cell surface.

Most B cells have the ability to secrete an antibody, also known as an immunoglobulin, a type of protein that can be secreted from or bound to the surface of B cells and recognize antigens. B cells secrete antibodies in response to infection with pathogens including parasites, viruses, and bacteria and mediate humoral immunity, an immune response characterized by antibodies circulating throughout the body.

Maturation of B Cells

B cells are formed and mature in bone marrow through V(D)J recombination and clonal selection. B cell maturation and differentiation is completed in the spleen.

The most important process that occurs to B cells in the bone marrow is V(D)J recombination, the process that generates specific B cell receptors. A series of gene rearrangement events results in some genes involved in antigen receptor generation being turned off while others remain turned on. This process happens independently in each B cell, and the end result is a population of B cells that all have different antigen receptors. V(D)J recombination occurs randomly and does not occur in response to a particular antigen. Beginning in the pre-B cell phase, the range of B cell antigen receptors is narrowed down through a selection process.

Some of the pre-B cells might recognize antigens from a person's own body instead of antigens that come from a pathogen or an infection. An important step that follows V(D)J recombination is clonal selection, a process that kills autoreactive immune cells, those that can induce an immune response against a person's own body and organs. Selection then proceeds to remove pre-B cells whose antigen receptors do not lead to cell signaling, and the B cells that remain have the capacity to recognize an infection. The V region, or variable region, is the part of the B cell antigen receptor protein that determines what antigen it can bind. The variable region is a part of the antigen binding site of an antibody, which consists of a constant domain and the variable region that binds to a target antigen.

Once a population of B cells that does not recognize a person's own cells has been developed in the bone marrow, these B cells migrate to the spleen. In the spleen, B cells finish maturing and can become any number of different kinds of mature B cells that have specific functions.

B Cells and Antibody Production

Different classes of B cells produce different antibodies with specialized functions that aid the immune reaction. B cells change the type of antibody they secrete through class switch recombination.
Several types of B cells are capable of secreting antibodies and do so at different points during their life cycle. Plasmablasts are activated early during an infection, rapidly secrete a lot of antibodies, and then die. Plasma cells are longer lived, synthesize and secrete large numbers of antibodies into circulation. Marginal zone B cells, follicular B cells, and plasma cells are types of longer-lived antibody-secreting cells that sustain the initial immune response against an infection. Memory B cells form over the course of an immune response through repeated exposure to an antigen. They are not involved in the initial immune response against a pathogen but have the unique capacity to secrete antibodies following a second infection with the same pathogen. Upon recognizing a pathogen during a secondary response, the immune response that occurs when the immune system encounters a pathogen a subsequent time, memory B cells rapidly proliferate and begin to secrete antibodies that recognize the pathogen. Regulatory B cells can suppress an inflammatory immune response following encounter with a pathogen by secreting molecules that suppress the activity of T cells.

Major Subclasses of B cells

B cell type Location Function
Plasmoblast Circulation Rapid antibody secretion early during infection
Plasma cell Circulation Long-term antibody secretion
Follicular Circulation, spleen, lymph nodes Mediate T cell immune response, differentiate into plasma cells
Marginal zone Spleen Evaluate antigens in circulation, transport antigen complexes to follicular cells
Regulatory Circulation Immunosuppression

Different types of B cells are found in different locations and have distinct roles.

B cells can make many different types of antibodies. The B cell receptor is an immunoglobulin molecule that is bound to the surface of a B cell. All B cells begin their life cycle making an antibody called IgM, which can be either secreted from B cells or bound to the surface of B cells and act like an antigen receptor. Signals made by other cells during an immune response can secrete molecules that activate B cells, and these activation signals can induce B cells to make other kinds of antibodies, such as IgA, IgG, and IgE, through the process of class switch recombination.

Class switch recombination is the capacity to change a specific part of each antibody molecule to replace the mu chain that forms the IgM antibody with a delta (D), alpha (A), gamma (G), or epsilon (E) chain to form each other antibody type. Each class of antibody is induced by different signals that are produced during immune responses to pathogens, such as chicken pox, influenza, and tuberculosis, or during a regulatory immune response that suppresses inflammation. IgE antibodies cause allergies, IgA antibodies are found in the gut and respiratory tract as well as in breast milk, and IgG is the most common type of antibody and is found in a variety of infections.

Structures of Antibodies

B cells can produce several different kinds of antibodies, each with a unique structure.