Antibody-independent B cell-intrinsic and -extrinsic roles for CD21/35.
Mice lacking C3, C4 or complement receptor 1/2 (Cr) have defective germinal centers (GC). The requirement for C4 implicates complement fixation by immune complexes (IC) via the classical pathway. Yet, transgenic (Tg) mice that lack circulating antibody but still express membrane IgM (mIgM) have normal GC responses. We showed previously that cross-linking mIgM leads to the deposition of C3 on the B cell surface and that disruption of this pathway diminishes GC responses. Here, we investigate the role of Cr in this process by generating mIgM-Tg mice that lack Cr and serum Ig. These mIgM/Cr-/- mice have smaller, transient GC, with incomplete B cell receptor down-regulation and peanut agglutinin up-regulation, compared to mIgM/Crwt counterparts. BM chimera experiments showed that Cr on B cells is required for normal GC responses. These results establish that Cr ligands generated at the B cell surface are sufficient for normal GC responses and function by signaling Cr on B cells. Unexpectedly, chimera experiments also showed a critical role for Cr on follicular dendritic cells (FDC), even in the absence of IC, indicating novel functions for FDC-expressed Cr beyond the capture of C3-coated IC.
Rossbacher
Joerg
J
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, USA.
Haberman
Ann M
AM
Neschen
Susanne
S
Khalil
Ashraf
A
Shlomchik
Mark J
MJ
D000818:Animals; D000906:Antibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003167:Complement Activation / Q000276:immunology*; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D017463:Receptors, Complement 3b / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D007075:Immunoglobulin M; D008565:Membrane Proteins; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d