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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 recruit innate immune killing mechanisms. Antibodies can also inhibit toxins such as those made by tetanus and diphtheria. Nearly all vaccines are designed to generate these 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 cancer and inflammatory and infectious 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. Unlike T cells, B-cell precursors differentiate into fully functional B cells in the bone marrow; they do not pass through the thymus. Like T cells, each mature B cell represents a clone, a group of cells that underwent the same heavy chain and light chain rearrangements to end up with the same B-cell receptor (BCR). And like T cells, B-cell clones undergo positive selection and negative selection to ensure that each mature naïve B cell that enters the circulation has a functional BCR that binds to self MHC and does not strongly bind self antigens. This B-cell clone’s BCR will be the basis for the antibodies produced by the clone’s offspring cells. 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, eds. Basic & Clinical Immunology. 7th ed. Originally published by Appleton & Lange. Copyright 1991, McGraw-Hill.)

B-CELL ACTIVATION

B cells constitute about 30% of the recirculating pool of small lymphocytes, and their life span is short (i.e., days or weeks). Within lymph nodes, they are located in follicles; within the spleen, they are found in the white pulp. They are also found ...

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