J Th2 cell

Dendritic cell ul

(or other isotype)

Activation of naive B cells

Secondary lymphoid tissues, regardless of location, contain regions predominantly populated by T cells or B cells. B cells predominate in follicles, while T cells are typically found in regions surrounding follicles (Fig. 8.2). Naive B-cell activation is initiated in the outer areas of follicles, where T-cell help is not limiting.

The initiating stimulus for B-cell activation is antigen-induced crosslinking of the B-cell receptor complex, followed by its endocytosis in a cytosolic endosome. Lysosomes fuse with the endosome and in so doing release their enzymatic contents (lysosomal enzymes), that degrade any antigen present. When cytosolic endosomes containing class II major histocompatibility complex molecules (MHC) fuse with antigen bearing endosomes a peptide/class II MHC complex is formed, which translocates to the B-cell surface (Chapter 3). This complex is recognized by differentiated, activated CD4+ T cells and leads to T-cell/B-cell conjugate formation, which is further stabilized by adhesion molecules (e.g., I-CAM I/LFA-1; LFA-3/CD2). Conjugate formation facilitates several membrane bound ligand interactions (e.g., B7/CD28; CD40/CD40 ligand) that together encompass B cell costimulatory signals. Activated naive B cells undergo clonal expansion that is detectable within 24 hours of immunization. Following the initial burst of proliferation, activated B cells and T cells migrate to primary follicles where enhanced proliferation of B cells leads to the formation of germinal centers, the hallmark of secondary follicles.

Fate of Activated B Cells in Germinal Centers

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