Some B cells migrate to form a primary focus and differentiate into plasmablasts, while some T cells induce Bcl-6 and become TFH cells TFH primary focus interfollicular zone CCL21 CXCL13 7˜,25-HC resting T cells resting B cells FDC dendritic cell Interactions with T cells sustain EBI2 expression on B cells, which move to outer follicular and interfollicular regions Activated B cells induce CCR7 and EBI2, and T cells induce CXCR5, and both cells migrate to follicular and interfollicular regions Before activation, resting B cells express CXCR5 and reside in follicles and T cells express CCR7 and reside in T-cell zones activated B cells activated T cells receptors, but its major actions in promoting survival are through BAFF-R (Fig. 10.6). BAFF-R signals through TRAF3 (see Section 3-7) to activate the non-canonical NFκB pathway, as described for CD40 (see Fig. 7.31), and, like CD40 signaling, induces expression of Bcl-2. Two other receptors for BAFF are TACI and BCMA, although BAFF has a relatively low affinity for BCMA. TACI and BCMA also bind the related cytokine APRIL, and they signal through TRAF2, 5, and 6 to induce signaling pathways involved in B-cell activation.
Antigens derived from microorganisms and viruses are transported into lymph nodes via the afferent lymph, and into the spleen via the blood. Opsonized antigens bearing C3b or C3dg accumulate in the B-cell follicles because they are trapped by complement receptors CR1 and CR2 expressed on the surface of FDCs. Opsonized particulate antigens can also be taken up by specialized macrophages residing in the subcapsular sinus (SCS) of lymph nodes and the marginal sinus of the spleen, regions that are both adjacent to the B-cell
BAFF (B-cell activating factor, also called B-lymphocyte stimulator, or BLyS) and APRIL (a proliferation-inducing ligand) are both members of the TNF superfamily of cytokines. They are initially produced as membrane-bound trimers by several cell types. BAFF is produced by FDCs and other cells in the B-cell follicle, where it supports B-cell survival. Its main receptor, BAFF-R, signals in a manner similar to CD40 (see Fig. 7.31) through TRAF3 and NIK to activate both the non-canonical NFκB pathway, leading to the RelB:p52 transcription factor, and the canonical p50:p65 NFκB pathway. BAFF also binds to the receptors TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BCMA (B-cell maturation antigen), although its affinity for the latter is relatively weak. These receptors activate the canonical NFκB pathway.
The low endocytic and Antigen preservation by