Secreted chondroitin sulfate proteoglycan of human B cell lines binds to the complement protein C1q and inhibits complex formation of C1.
We recently characterized a species of proteochondroitin sulfate (CSPG) secreted by human B cell lines that closely resembles in its structure the serum-derived C1q inhibitor (C1qI). These proteoglycans have in common a molecular mass of approximately 130 to 150 kDa with a core protein of 30 kDa to which up to four chondroitin sulfate chains each of approximately 26 kDa are attached. Since this B cell-derived CSPG is a potential source for serum C1qI, we measured its capacity to interact with C1q in solid-phase binding and complex electrophoresis assays. B cell CSPG purified from culture supernatants of the two human B cell lines JOK-1 and U266 strongly bound to C1q. In contrast to the secreted form, cellular proteoglycan of the myeloma cell line U266 did not interact with C1q. Binding of C1q to CSPG was competitively inhibited by free glycosaminoglycans (GAG) in the order dextran sulfate > heparin > heparan sulfate > chondroitin-6-sulfate (CS-C) > dermatan sulfate (CS-B) > chondroitin-4-sulfate (CS-A). B cell CSPG inhibited the hemolytic activity of C1q and C1. In addition, B cell CSPG blocked C1q receptor binding in a dose-dependent manner. The proteoglycans did not influence the activity of C1 complex already bound to EAC4 target cells. By interaction of CSPG with solid-phase-bound C1q, formation of the C1 complex upon the addition of C1r and C1s was impaired. Strong binding of B cell CSPG to C1q, its inhibition of C1q activity, and its structural similarities to the previously described human serum C1qI indicate that B cells produce a soluble CSPG, which may act as C1qI under physiologic conditions.
Kirschfink
M
M
Institute of Immunology, University of Heidelberg, Germany.
Blase
L
L
Engelmann
S
S
Schwartz-Albiez
R
R
D001402:B-Lymphocytes / Q000378:metabolism*; D001667:Binding, Competitive; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D003172:Complement C1 / Q000378:metabolism*; D015922:Complement C1q / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015923:Complement C1r / Q000378:metabolism; D003173:Complement C1s / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D046911:Macromolecular Substances; D011485:Protein Binding
D011508:Chondroitin Sulfate Proteoglycans; D003172:Complement C1; D046911:Macromolecular Substances; D015922:Complement C1q; D015923:Complement C1r; D003173:Complement C1s