The B cell receptor itself can activate complement to provide the complement receptor 1/2 ligand required to enhance B cell immune responses in vivo.
B cells express complement receptors (CRs) that bind activated fragments of C3 and C4. Immunized CR knockout (KO) mice have lower antibody titers and smaller germinal centers (GCs), demonstrating the importance of CR signals for the humoral immune response. CR ligands were thought to be generated via complement fixation mediated by preexisting "natural" IgM or early Ab from inefficiently activated B cells. This concept was recently challenged by a transgenic (Tg) mouse model that lacks circulating antibody but still retains membrane IgM (mIgM) and mounts normal immune responses. To test whether CR ligands could be generated by the B cell receptor (BCR) itself, we generated similar mice carrying a mutated mIgM that was defective in C1q binding. We found that B cells from such mutant mice do not deposit C3 on B cells upon BCR ligation, in contrast to B cells from mIgM mice. This has implications for the immune response: the mutant mice have smaller GCs than mIgM mice, and they are particularly deficient in the maintenance of the GC response. These results demonstrate a new BCR-dependent pathway that is sufficient and perhaps necessary to provide a CR1/2 ligand that promotes efficient B cell activation.
Rossbacher
Joerg
J
Serction of Immunobiology and Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520-8035, USA.
Shlomchik
Mark J
MJ
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003167:Complement Activation / Q000502:physiology*; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007114:Immunization; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism*
D000941:Antigens; D007075:Immunoglobulin M; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D011951:Receptors, Complement; D003165:Complement System Proteins