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 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.
Fischer
M B
MB
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Ma
M
M
Goerg
S
S
Zhou
X
X
Xia
J
J
Finco
O
O
Han
S
S
Kelsoe
G
G
Howard
R G
RG
Rothstein
T L
TL
Kremmer
E
E
Rosen
F S
FS
Carroll
M C
MC
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D010584:Bacteriophage phi X 174 / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency; D003181:Complement C4 / Q000172:deficiency; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000494:pharmacology*; D005260:Female; D018858:Germinal Center / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D003176:Complement C3; D003181:Complement C4; D003165:Complement System Proteins