B‐CELLS RESPOND TO THREE DIFFERENT TYPES OF ANTIGEN
There are three main types of B‐cell that respond to infection by secreting antibodies that target specific classes of microbes, with the particular function of each B‐cell subset generally determined by their location. Follicular B‐cells (also called B2 cells) express highly specific monoreactive B‐cell receptors (BCRs), are present in the lymphoid follicles of the spleen and lymph nodes, and typically require T‐cells in order to generate high‐affinity antibodies, and to undergo class switching (Figure 7.21). However, as we shall discuss below, certain types of antigens (called T‐independent antigens) can promote B‐cell activation without the help of T‐cells. The antibodies thus formed are typically of low affinity and do not undergo class switching or somatic hypermutation but provide rapid protection from certain microorganisms and buy time for T‐dependent B‐cell responses to be made. Such rapid antibody responses are mediated by the “innate like” B‐cells; B1 and marginal zone (MZ) B‐cells, which express polyreactive BCRs that are of broad specificity and enable them to recognize multiple different kinds of evolutionarily conserved microbial antigens. In this way, they are similar to the Toll‐like receptors (TLRs) expressed on conventional innate immune cells. Indeed, innate‐like B‐cells also express TLRs and can be directly activated by PAMPs, act as APCs, and secrete cytokines, which places them at the interface between the innate and adaptive immune systems. Importantly, this innate‐like B‐cell response is positioned at strategic areas that are sensitive to microbial invasion, such as the skin, mucosa, and the marginal zone of the spleen, where the lymphatic and circulatory systems converge.