Regulation of the B cell response to T-dependent antigens by classical pathway complement
Fischer, M.B.; Ma, M.; Goerg, S.; Zhou, X.; Xia, J.; Finco, O.; Han, S.; Kelsoe, G.; Howard, R.G.; Rothstein, T.L.; Kremmer, E.; Rosen, F.S.; Carroll, M.C.
Journal of Immunology 157(2): 549-556
1996
ISSN/ISBN: 0022-1767 PMID: 8752901 Document Number: 459804
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 demonstrated a diminished level of peanut agglutinin+ germinal centers and a failure in isotype switching despite normal B cell signaling in 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 those 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 the hypothesis that covalent attachment of complement ligands, i.e., C3b and C3d to the Ag-Ab complex, increases its immunogenicity.