Regulation of B Cell Receptor-Mediated MHC Class II Antigen Processing by FcγRIIB1

The processing and presentation of Ag by Ag-specific B cells is highly efficient due to the dual function of the B cell Ag receptor (BCR) in both signaling for enhanced processing and endocytosing bound Ag. The BCR for IgG (FcγRIIB1) is a potent negative coreceptor of the BCR that blocks Ag-induced B cell proliferation. Here we investigate the influence of the FcγRIIB1 on BCR-mediated Ag processing and show that coligating the FcγRIIB1 and the BCR negatively regulates both BCR signaling for enhanced Ag processing and BCR-mediated Ag internalization. Treatment of splenic B cells with F(ab′) 2 anti-Ig significantly enhances APC function compared with the effect of whole anti-Ig; however, whole anti-Ig treatment is effective when binding to the FcγRIIB1 was blocked by a FcγRII-specific mAb. Processing and presentation of Ag covalently coupled to anti-Ig were significantly decreased compared with Ag coupled to F(ab′) 2 anti-Ig; however, the processing of the two Ag-Ab conjugates was similar in cells that did not express FcγRIIB1 and in splenic B cells treated with a FcγRII-specific mAb to block Fc binding. Internalization of monovalent Ag by B cells was reduced in the presence of whole anti-Ig as compared with F(ab′) 2 anti-Ig, but the internalized Ag was correctly targeted to the class II peptide loading compartment. Taken together, these results indicate that the FcγRIIB1 is a negative regulator of the BCR-mediated Ag-processing function.