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Activated B regulatory cells (Bregs) also secrete immunosuppressive cytokines IL‐10, IL‐35 and TGF‐β. IL‐10 and IL‐35 render CD4 Th1 and Th17 cells incapable of mediating immunopathology or producing proinflammatory cytokines [12]. In contrast, Breg secretion of TGF‐β promotes antigen‐activated CD4 T‐cell differentiation into iTregs (Figure 2.2), secreting IL‐10 that inhibits TNF‐α production. Additional mechanisms also contribute to B‐cell immunoregulation. Secreted IgM induces anti‐inflammatory apoptotic bodies to reduce proinflammatory cytokines. Contact between B and CD4 T cells reduces CD4 T‐cell proliferation and secretion of Th1. Binding of B cell CD95L (Fas ligand) to CD95 (Fas) on T cells induces T‐cell apoptosis. Secretion of autoantigen‐specific IgG4 inhibits ADCC, C′ activation, and formation of immune complexes because of the low affinity of IgG4 for Fc receptors, low capacity to activate C′, and its competition with other antibodies.