Complement activation by cross-linked B cell-membrane IgM.
The B cell membrane IgM (mIgM) occurs in a monomeric form incapable of activating C. However, when cross-linked by a polyvalent ligand, mIgM may activate C by assuming a polymeric structure like secreted IgM. This possibility was tested with CR2- lymphoma cells, which did not activate C spontaneously. When CR2-deficient mIgM(lambda)+ Ramos cells were treated with F(ab')2 goat anti-lambda, then exposed to human serum, a marked C3 deposition took place, as examined by the flow cytometry. Similarly, C3 deposition on mIgM(kappa)+, mIgD(kappa)+ P32 cells was induced by F(ab')2 of either anti-kappa or anti-mu. Anti-delta was without effect, but the C3 deposition resulting from anti-kappa was markedly enhanced after mIgD was modulated by anti-delta. The mIgM-cross-linked cells bound C1q, and C3 deposition on these cells was abrogated by depletion of C1q, but not Factor B nor D, from serum. The C1-binding step of the mIgM-mediated C activation was inhibited by monomeric Fab' of polyclonal anti-mu containing a blocking Ab to the hemolytic activity of human IgM Forssman Ab. A large proportion of C3 deposits on mIgM-cross-linked cells was found to be associated with mIgM in the form of C3dg or C3d. These results demonstrate that cross-linked mIgM indeed triggers the classical pathway of C.
Ohishi
K
K
Department of Microbiology, Ehime University School of Medicine, Japan.
Kanoh
M
M
Shinomiya
H
H
Hitsumoto
Y
Y
Utsumi
S
S
D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D015922:Complement C1q / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism*; D003171:Complement Pathway, Classical / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003176:Complement C3; D007075:Immunoglobulin M; D008565:Membrane Proteins; D015922:Complement C1q