Fig. 4

IgE isotype switching in B cells. The surface immunoglobulin that serves as the B-cell antigen receptor (BCR) has two roles in B-cell activation. First, in combination with the BCR co-receptors, it transmits signals directly to the cell’s interior when it binds antigen (event 1). Second, the B-cell antigen receptor delivers the antigen to intracellular sites where it is degraded and returned to the B-cell surface as peptides bound to MHC class II molecules (event 2). Subsequent isotype switching of B cells to IgE production is induced by two separate signals, both of which can be provided by polarized Th2 cells. The first signal is provided by the cytokine IL-4 interacting with the IL4 receptor on the B cells (event 3), which leads to activation of STAT-6 (event 4). The second signal for IgE switching is a co-stimulatory CD40-CD40L interaction (event 5). Both signals are important for the initiation of the antibody class switching (event 6), resulting in IgE production (event 7). It is also possible to induce a CD40-independent induction of isotype switching which involves the interaction of BAFF-BAFFR and APRIL-TACI interactions between DC and B cells (event 8)