Fig. 10.3 TFH cells provide several signals that activate B cells which activates the transcription factor STAT3 to enhance B-cell and control their subsequent differentiation. After antigen proliferation and survival. TFH cells can also produce cytokines that binding to the B-cell receptor delivers the first signal for B-cell will regulate isotype switching (see Section 10-12). After receiving activation (not shown), the TFH cell delivers additional signals these signals, activated B cells begin to proliferate (second panel), when it recognizes a peptide:MHC class II complex on the B-cell enter the germinal center, and eventually become plasma cells or surface (first panel). Besides expression of CD40 ligand, the TFH cell memory B cells (third panel). secretes several important cytokines. Included among them is IL-21, 10-2 Linked recognition of antigen by T cells and B cells promotes robust antibody responses.
B-cell activation by antigens on microbial surfaces can be greatly stimulated by the concurrent deposition of complement on these pathogens. The B-cell co-receptor complex contains the cell-surface proteins CD19, CD21, and CD81 (see Fig. 7.27). When CD21, or complement receptor 2 (CR2), binds to the complement fragments C3d and C3dg that are deposited on microbial surfaces (see Section 2-13), it is brought near to the activated B-cell receptor bound to the same surface. CD21 and CD19 are associated with each other, and CD19 becomes phosphorylated by the activated B-cell receptor. This recruits PI 3-kinase, which then stimulates several downstream pathways, enhancing proliferation, differentiation, and antibody production (see Fig. 10.2, arrow 1). This effect is shown dramatically when mice are immunized with the experimental antigen hen egg-white lysozyme that is coupled to three linked molecules of C3dg. In this case the dose of modified lysozyme needed to induce antibody in the absence of added adjuvant is as little as 1/10,000 of that needed with the unmodified lysozyme.
For T-dependent antibody responses, the T cells involved are activated by the same antigen as is recognized by the B cells; this is called linked recognition. However, the peptide recognized by the TFH cell is likely to differ from the protein epitope recognized by the B cell’s antigen receptor. Natural antigens, such as viruses and bacteria, contain multiple proteins and carry both protein and carbohydrate epitopes. For linked recognition to occur, the peptide recognized by the T cell must be physically associated with the antigen recognized by the B cell’s receptor, so that the B cell can take up and present the appropriate peptide to the T cell. For example, a B cell that recognizes an epitope on a viral coat protein will internalize the complete virus particle. The B cell can degrade multiple viral proteins into peptides for display on MHC class II molecules on the B-cell surface. CD4 T cells specific for such viral peptides may have been activated by dendritic cells earlier in the infection, and some will have differentiated into TFH cells. When these TFH cells are activated by B cells presenting their peptide, they are stimulated to provide specific signals that help B cells to generate antibodies against the viral coat protein (Fig. 10.4).