Modulation of the humoral immune response by antibody-mediated antigen targeting to complement receptors and Fc receptors

During an ongoing immune response, immune complexes, composed of Ag, comple ment factors, and Igs, are formed that can interact with complement recepto rs (CRs) and IgG Fc receptors (Fc gamma R), The role of CR1/2 and Fc gamma R in the regulation of the immune response was investigated using OVA that was chemically conjugated to whole Ige of the rat anti-mouse CR1/2 mAb 7G6, FAGS analysis using the murine B cell lymphoma IIA1.6 confirmed that the 7 G6-OVA conjugate recognized CR1/2. Incubating IIA1.6 cells with 7G6-OVA tri ggered tyrosine phosphorylation and Ag presentation to OVA-specific T cells in vitro. Immunizing mice with 7G6-OVA at a minimal dose of 1 mu g i.p. pe r mouse markedly enhanced the anti-OVA Ig response, which was primarily of the IgG1 isotype subclass. The 7G6-OVA did not enhance the anti-OVA respons e in CR1/2-deficient mice. OVA coupled to an isotype control Ab induced a c onsiderably lower anti-OVA response compared with that induced by OVA alone , suggesting inhibition by interaction between the Fc part of the Ab and th e inhibitory Fc gamma RIIb on B cells. This finding was supported by the ob servation that IIA1.6 cells which were incubated with 7G6-OVA lost the abil ity to present Ag upon transfection with Fc gamma RIIb, In sum, 7G6-conjuga ted OVA, resembling a natural immune complex, induces an enhanced anti-OVA immune response that involves at least CR1/2-mediated stimulation and that may be partially suppressed by Fc gamma RIIb.