Rat polymeric IgA binds C1q, but does not activate C1.
Immune complexes, prepared with monoclonal rat IgA antibodies directed against DNP, activate the alternative pathway of the complement system in rat serum. In this study, the interaction of these monoclonal IgA antibodies with the classical pathway of complement was investigated. Monoclonal polymeric IgA (p-IgA) was shown to inhibit the IgG2b-mediated classical pathway-dependent lysis of TNP-coated sheep red blood cells. In addition, the binding of C3 to solid phase IgG2b immune complexes was inhibited by p-IgA. Monoclonal monomeric IgA (m-IgA) was much less efficient in this respect. To further analyse the effect of p-IgA on the activation of the classical pathway by IgG2b immune complexes, the interaction of p-IgA with C1 was studied. It was found that p-IgA antibodies bind C1q. No species-specificity was observed, since both rat and human C1q were bound. Whereas binding of C1q in C1 to IgG2b resulted in activation of C1, binding to p-IgA did not. The binding of C1q to both p-IgA and IgG2b could be inhibited by monoclonal antibodies directed against the globular heads of C1q, but not by monoclonal antibodies directed against the collagen tail. The formation of insoluble p-IgA immune complexes was inhibited in the presence of rat serum or C1. These studies indicate that C1q binds to p-IgA by its globular heads, and thereby may modulate classical pathway-mediated reactions such as the inhibition of immune precipitate formation.
Hiemstra
P S
PS
Department of Nephrology, University Hospital Leiden, The Netherlands.
Rits
M
M
Gorter
A
A
Stuurman
M E
ME
Hoekzema
R
R
Bazin
H
H
Vaerman
J P
JP
van Es
L A
LA
Daha
M R
MR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001704:Biopolymers; D003167:Complement Activation / Q000276:immunology*; D003172:Complement C1 / Q000276:immunology*; D015922:Complement C1q / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism; D003171:Complement Pathway, Classical; D006461:Hemolysis; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D007477:Ions; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001704:Biopolymers; D003172:Complement C1; D003176:Complement C3; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D007477:Ions; C034639:polymeric IgA; D015922:Complement C1q