DISRUPTION OF THE CR-2 LOCUS RESULTS IN A REDUCTION IN B-1A CELLS ANDIN AN IMPAIRED B-CELL RESPONSE TO T-DEPENDENT ANTIGEN

Covalent attachment of activated products of the third component of co mplement to antigen enhances its immunogenicity, but the mechanism is not clear. This effect is mediated by specific receptors, mCR1 (CD35) and mCR2 (CD21), expressed primarily on B cells and follicular dendrit ic cells in mice. To dissect the role of mCR1 and mCR2 in the humoral response, we have disrupted the Cr2 locus to generate mice deficient i n both receptors. The deficient mice (Cr2(-/-)) were found to have a r eduction in the CD5(+) population of peritoneal B-1 cells, although th eir serum IgM levels were within the range of normal mice. Moreover, C r2(-/-) mice had a severe defect in their humoral response to T-depend ent antigens that was characterized by a reduction in serum antibody t iters and in the number and size of germinal centers within splenic fo llicles. Reconstitution of the deficient mice with bone marrow from MH C-matched Cr2(+/+) donors corrected the defect, demonstrating that the defect was due to B cells themselves. These results indicate an oblig atory role of B cell complement receptors in responses of the B cells to protein antigens.