Some plasma cells deriving from germinal centers in lymph nodes or spleen migrate to the bone marrow, where a subset live for a long period, whereas others migrate to the medullary cords in lymph nodes or splenic red pulp. B cells that have been activated in germinal centers in mucosal tissues, and which are predominantly switched to IgA production, stay within the mucosal system. A splice variant of XBP1 (X-box binding protein 1) is expressed in plasma cells and helps to regulate their secretory capacity. Plasma cells in bone marrow receive signals from stromal cells that are essential for their survival, and they can be very long lived, whereas plasma cells in the medullary cords or red pulp are not long lived. XBP1 is also required for plasma cells to colonize bone marrow successfully. Plasma cells in the bone marrow are the source of long-lasting high-affinity class-switched antibody.
Other germinal center B cells differentiate into memory B cells. Memory B cells are long-lived descendants of cells that were once stimulated by antigen and had proliferated in the germinal center. They divide very slowly if at all; they express surface immunoglobulin but secrete no antibody, or do so only at a low rate. Because the precursors of some memory B cells arise from the germinal center reaction, memory B cells can inherit the genetic changes that occur there, including somatic hypermutation and the gene rearrangements that result in a class switch. The signals that control which path of differentiation a B cell takes are still being investigated. We will briefly return to memory B cells in Chapter 11.
10-14 Some antigens do not require T-cell help to induce B-cell responses.
Humans and mice with T-cell deficiencies are able to produce antibodies against thymus-independent (TI) antigens, which we introduced in Section 10-1. These antigens include certain bacterial polysaccharides, polymeric proteins, and lipopolysaccharides, which are able to stimulate naive B cells in the absence of T-cell help. These nonprotein bacterial products cannot elicit classical T-cell responses, yet they induce antibody responses in normal individuals. In addition, there are TI antigens that are not derived from bacteria; these include plant-derived mitogens and lectins, viral antigens, and superantigens, and some parasite-derived antigens.
Thymus-independent antigens fall into two classes, TI-1 and TI-2, which activate B cells by two different mechanisms. TI-1 antigens rely on activity that can directly induce B-cell division without T-cell help. We now understand that TI-1 antigens contain molecules that cause the proliferation and differentiation of most B cells regardless of their antigen specificity; this is known as polyclonal activation (Fig. 10.24, top panels). TI-1 antigens are therefore
Fig. 10.24 TI-1 antigens induce polyclonal B-cell responses at high concentrations, and antigen-specific antibody responses at low concentrations. At high antigen concentration, the signal delivered by the B-cell-activating moiety of TI-1 antigens is sufficient to induce B-cell proliferation and antibody secretion in the absence of specific antigen binding to surface immunoglobulin. Thus, all B cells respond (top panels). At low concentration, only B cells specific for the TI-1 antigen bind enough of it to focus its B-cell activating properties onto the B cell; this gives a specific antibody response to epitopes on the TI-1 antigen (lower panels).