Control of C3b and C5b deposition by CD46 (membrane cofactor protein) after alternative but not classical complement activation.
C3b and C5b deposition following complement activation, and its regulation by CD46 were studied using xenogenic Chinese hamster ovary (CHO) cells as targets and cytofluorometry. Following activation of the alternative pathway, an initial low level of C3b deposition was observed on CHO cell surfaces after a lag time of approximately 4 min. This was followed by a secondary high level of C3b deposition with a slower rate. C3b deposition was maximal within 15 min. When CD46 was expressed (B2 isoform), the kinetics of C3b deposition were essentially unchanged, but the onset of the secondary high C3b deposition was fully prevented. C5b deposition was also observed on CHO but not on CHO.CD46 cells following activation of the alternative pathway. Activation of the classical pathway on CHO and CHO.CD46 cells, using factor B-depleted human serum and anti-CHO antibodies, resulted in almost identical single-peak C3b deposition profiles. Accordingly, no regulation of C5b deposition by CD46 was evident following activation of the classical pathway. These data indicate that CD46 prevents the C3b deposition amplification loop mediated by the alternative C3 convertase and, consequently, inhibits the formation of the alternative C5 convertase. But CD46 prevents neither the spontaneous tick-over C3b deposition leading to the formation of the alternative C3 convertase nor the formation of the functional classical C3 and C5 convertases.
Devaux
P
P
Immunité & Infections Virales, IVMC, CNRS-UCBL UMR 5537, Lyon, France.
Christiansen
D
D
Fontaine
M
M
Gerlier
D
D
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D016466:CHO Cells; D003167:Complement Activation / Q000276:immunology*; D003179:Complement C3b / Q000276:immunology*; D003182:Complement C5 / Q000276:immunology*; D050776:Complement C5b; D003169:Complement Inactivator Proteins / Q000276:immunology*; D006224:Cricetinae; D006801:Humans; D007700:Kinetics; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D015703:Antigens, CD; C497857:CD46 protein, human; D003182:Complement C5; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D003179:Complement C3b; D050776:Complement C5b