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T-independent, mainly IgM; short-lived plasma cells

FIGURE 11-3 Distinct B cell subsets mediate different types of antibody responses. Follicular B cells are recirculating cells that receive T cell help when they respond to protein antigens and thus initiate T-dependent antibody responses. These responses can lead to the formation of germinal centers, where class switching and somatic mutation of antibody gene occur, resulting in specialized high-affinity antibody responses. T-independent responses to multivalent antigens such as lipids, polysaccharides, and nucleic acids are mediated mainly by marginal zone B cells in the spleen and B-1 cells in mucosal sites. These functional distinctions between subsets are not absolute.

course, is one of the important distinctions between the forms of antigens recognized by B and T lymphocytes (see Chapter 6).

Activation of B Cells by Antigens and Other Signals

The activation of antigen-specific B lymphocytes is initiated by the binding of antigen to membrane Ig molecules, which, in conjunction with the associated Iga and Igp proteins, make up the antigen receptor complex of mature B cells. The B lymphocyte antigen receptor, described in Chapter 7, serves two key roles in B cell activation. First, binding of antigen to the receptor delivers biochemical signals to the B cells that initiate the process of activation (see Chapter 7). Second, the receptor internalizes the bound antigen into endosomal vesicles, and if the antigen is a protein, it is processed into peptides that may be presented on the B cell surface for recognition by helper T cells. This antigen-presenting function of B cells will be considered later in the context of T-dependent B cell activation.

Although antigen recognition can initiate B cell responses, by itself it is usually inadequate to stimulate significant B cell proliferation and differentiation. For full responses to be induced, other stimuli cooperate with BCR engagement, including complement proteins, pattern recognition receptors, and, in the case of protein antigens, helper T cells (discussed later).

B cell activation is facilitated by the CR2/CD21 core-ceptor on B cells, which recognizes complement fragments covalently attached to the antigen or that are part of immune complexes containing the antigen (Fig. 11-5). Complement activation is typically seen with microbes, which activate this system in the absence of antibodies by the alternative and lectin pathways, and in the presence of antibodies by the classical pathway (see Chapters 4 and 12). In all these situations, complement fragments are generated that bind to the microbes. One of these fragments, called C3d, is recognized by the complement receptor CR2 (also called CD21), which enhances the strength of BCR signaling and thus functions as a core-ceptor for B cells (see Chapter 7). Some nonmicrobial polysaccharides also activate complement by the alternative or lectin pathway, and this is one reason that such antigens are able to induce antibody responses without T cell help.

Microbial products engage Toll-like receptors on B cells, which also enhances B cell activation (see Fig. 11-5). Human B cells express several Toll-like receptors (TLRs), including TLR5, which recognizes bacterial flagellin; endosomal TLR7, which recognizes single-stranded RNA; and TLR9, which is specific for unmethylated CpG-rich DNA in endosomes (see Chapter 4). Murine B cells also express TLR4 on the cell surface. These pattern recognition receptors directly activate B cells. In addition, the activation of myeloid cells through pattern recognition receptors can promote B cell activation indirectly in two ways. Dendritic cells activated through TLRs contribute significantly to helper T cell activation (see Chapter 9). Myeloid cells activated by TLRs may secrete APRIL and BAFF, cytokines that can induce T-independent B cell responses.

Subcapsular sinus

Antigen arrives from tissues via afferent lymphatics

Subcapsular sinus

Antigen arrives from tissues via afferent lymphatics

Macrophage in subscapular sinus

* mm Follicle

FIGURE 11-4 Pathways of antigen delivery to follicular B cells. Antigen is delivered to B cells in follicles largely through afferent lymphatics that drain into the subcapsular sinus of the lymph node. Small antigens may reach the follicle through conduits. Larger antigens may be captured by subcapsular sinus macrophages and delivered to the follicle, or they may directly access dendritic cells in the medulla that may be involved in delivering antigen not only to the T cell zone but also to B cell-containing follicles.

Macrophage in subscapular sinus

Dendritic cells in medulla

* mm Follicle y Larger antigens taken up by macrophages in subcapsular sinus and by dendritic cells in medulla

FIGURE 11-4 Pathways of antigen delivery to follicular B cells. Antigen is delivered to B cells in follicles largely through afferent lymphatics that drain into the subcapsular sinus of the lymph node. Small antigens may reach the follicle through conduits. Larger antigens may be captured by subcapsular sinus macrophages and delivered to the follicle, or they may directly access dendritic cells in the medulla that may be involved in delivering antigen not only to the T cell zone but also to B cell-containing follicles.

Dendritic cells in medulla

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