See also T cell activaiton in immune cells

Antigen recognition by B cells is mediated by the B cell receptor (BCR), a surface-bound immunoglobulin in complex with signaling componets CD79alpha and CD79beta. Crosslinking of BCR upon engagement of antigen results in phosphorylation of immunoreceptor tyrosin-based activation motifs (ITAMs) within CD79 a and CD79b, initiating a cascade of intracellular signaling events that recruits downstream molecules to the membrane and stimulate calcium mobilization. This leads to the induction of diverse B cell responses (e.g., cell suvival, proliferation, antibody production, antigen presentation, differentiation, etc) which lead to a humoral iimmune response. Other components of the BCR coreceptor complex ehnace (e.g., CD19, CD21, and CD81) or suppress (e.g., CD22 and CD72) BCR activation signals. (Chu, US 2012/0321620).

Negative feedback of BCR

Antibody negative feedback

When antibodies are produed to an antigen, the circulating level of immune complexes (e.g., antigen bound to antibody) increases. These imune complexes downregulate antigen-induced B cell activation. It is believed that these immune complexes downregulate antigen-induced B cell activaiton by coengaging cognate BCR with the low-affinity inhibitory receptor Fc.gamma.RIIb, the only IgG receptor on the B cells. It is also beleived that this negative feedback of antibody production requires interaction of the antibody Fc domain with FcgammaRIIb since immune complexes containing (F(ab’).sub.2 antibody fragmetns are not inhibitory. The intracellular immunoreceptor tyrosine-based inhibitory. motif (ITIM) of Fc.gamma.RIIb is necessary to inhibit BCR induced intracellular signals. This inhibitory effet occurs through phosphorylation of teh Fc.gamma.RIIb ITIM, which recurits SH2-containing inositol polyphosphate 5-phosphatase (SHIP) to neutralize ITAM-induced intracellular calcium mobilization. In addition, Fc.gamma.RIIb-mediated SHIP phosphorylation inhibits the downstream Ras-MAP proliferation patway.. (Chu, US 2012/0321620). 

Chu, US 2012/0321620) disclosees immunoglobulins that inhibit cells that ewxpress Fc.gamma.RIIb. The antibodies binds Fc.gamma.RIIb and coengages a target antigen on the cell’s surface and coengages a target antigen on the cell’s surface and an Fc.gamma.RIIb on the cell’s surface.