Acceleration of site-to-site transfer of C1- by a monoclonal antibody to C1-s.
A monoclonal antibody to human C1-s (a subcomponent of C1-), M365 blocked the complement-mediated lysis of C1(-)-coupled IgM-sensitized sheep erythrocytes (EAIgMC1). However, M365, via its binding to C1-s, did not inhibit C2 activation and only partially inhibited C4 activation, both attributable to the proteolytic action of C1s. Therefore, the inhibition of lysis of EAIgMC1 is not due to the direct effect of antibody binding to C1-s in the C1- molecule. M365, when added to the pre-formed EAIgMC1, deprived the whole C1 molecule from the cells. It was also found that M365-bound C1 could not bind to EAIgM. These phenomena were induced only when M365, one of seven monoclonal antibodies to C1-s, was employed and when IgM antibody-sensitized E was used. The observed C1- liberation and C1 binding inhibition by M365 were found to be less effective when the C4b bearing cells, EAIgMC4, were used. But the addition of M365-bound C1- to EAIgMC4 promoted the formation of the C3 convertase, C4b2a, which caused an incremental lysis of the C4b bearing cells. The results are interpreted to mean that C1-, once complexed with M365, still remains active and acquires the ability to transfer from one C1 binding site on IgM to another to activate the convertases. C4b must be a prerequisite on the cells to induce the effective C1- transfer and resulting increase of C3 convertase sites. We hypothesize that the M365-C1-s association alters the conformation of C1q and thereby leads to the dissociation of whole C1- from IgM. The M365-C1- complex, therefore, can move from site to another.
Matsumoto
M
M
Department of Immunology, Center for Adult Diseases Osaka, Japan.
Nagaki
K
K
Seya
T
T
Kitamura
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D003167:Complement Activation; D003172:Complement C1 / Q000276:immunology / Q000378:metabolism*; D003173:Complement C1s / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006461:Hemolysis; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003172:Complement C1; D007075:Immunoglobulin M; D003173:Complement C1s