REGULATION OF THE B-CELL RESPONSE TO T-DEPENDENT ANTIGENS BY CLASSICAL PATHWAY COMPLEMENT

Mice deficient in complement components C3 (C3-/-) and C4 (C4-/-) were found to have a profound defect in their Ab response to a T-dependent Ag (bacteriophage phi X174). Characterization of the deficient mice d emonstrated a diminished level of peanut agglutinin(+) germinal center s and a failure in isotype switching despite normal B cell signaling i n vitro. The nature of the defect was found to lie at the B cell level , as the T cells were primed in C3- and C4-deficient mice as well as t hose in wild-type mice. These results, and the finding that the defect could be partly reversed by a 10-fold increase in Ag dose, support th e hypothesis that covalent attachment of complement ligands, i.e., C3b and C3d to the Ag-Ab complex, increases its immunogenicity.