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INTRODUCTION

B cells perform two important functions: (1) they differentiate into plasma cells that produce antibodies and (2) they differentiate into long-lasting memory cells that respond robustly and rapidly to reinfection.

Antibodies are the principal defense used by the immune system to prevent infection because, by binding to the microbes’ surfaces, they can inhibit them from attaching to target cells and/or help innate killing mechanisms. Antibodies can also inhibit toxins such as those made by tetanus and diphtheria. Vaccines work by raising protective, or neutralizing, antibodies.

Advances in cell biology have allowed the generation of large quantities of engineered monoclonal antibodies. The ability of these antibodies to strongly bind a specific antigen with very limited “cross-reactive” binding of other antigens is the basis for many common diagnostic tests and an increasing array of therapies for various diseases (see Monoclonal Antibodies section later in this chapter).

B-CELL MATURATION

As described in Chapter 59, B cells come from stem cells called common lymphoid progenitors, which give rise to all lymphocytes. Each mature B cell represents a clone, a group of cells arising from a precursor, all of which have the same heavy chain and light chain rearrangements to form the same B-cell receptor (BCR). Because the BCR—and secreted antibodies—from the clone and its progeny all have the same antigen specificity, these antibodies are called monoclonal. Figure 61–1 depicts an overview of the phases of B-cell maturation.

FIGURE 61–1

Maturation of B cells. B cells arise from lymphoid progenitor stem cells and differentiate into pre-B cells expressing μ heavy chains in the cytoplasm and then into mature B cells expressing monomer IgM on the surface. This occurs independent of antigen. Activation of B cells, class switching, and differentiation into memory B cells and plasma cells occurs after exposure to antigen (red star) and is enhanced by T-cell help. μ = mu heavy chains in cytoplasm; Y = IgM (blue) or IgG (purple). (Adapted with permission from Stites DP, Terr A: Basic & Clinical Immunology, 7th ed. New York, NY: McGraw Hill; 1991.)

B-CELL ACTIVATION

B cells constitute about 30% of circulating lymphocytes. In lymph nodes, they are located in follicles; in the spleen, they are located in the white pulp. They are also found in gut-associated lymphoid tissue (GALT) such as Peyer’s patches. They express the chemokine receptor CXCR5, which guides them toward chemokines produced in a region called the B-cell follicle. B cells reside in the follicles and survey the lymph and bloodstream for antigens.

After binding an antigen, B cells are stimulated to proliferate and “class switch.” Like T cells, B cells generally require two signals to become activated. Signal 1 is ...

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