The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells.
Normal human B lymphocytes are known to activate the alternative pathway (AP) of complement, leading to C3-fragment deposition and membrane attack complex (MAC) formation. The process is mediated via complement receptor type 2 (CR2, CD21), with complement receptor type 1 (CR1, CD35) playing a subsidiary role. In this study, we examine the relative contributions of CR1 and CR2 to the deposition of C3 fragments and MAC on B lymphocytes under circumstances where all complement pathways are operational. C3-fragment deposition and MAC formation were assessed on human peripheral B lymphocytes in the presence of 30% autologous serum. Blocking the CR2 ligand-binding site with monoclonal antibody (mAb) FE8 resulted in significant reduction (37.9+/-11.9%) in C3-fragment deposition, whereas MAC formation was only marginally affected (12.1+/-22.2% reduction). Blocking the CR1 binding-site resulted in significant reduction of both C3-fragment deposition (22.0+/-14.5%) and MAC formation (47.4+/-13.8%). Both the lack of CR2 influence on MAC formation and the promotion of C3-fragment deposition by CR1 are in striking contrast to the situation where only the AP is operational. The presence of erythrocytes (E) bearing CR1, however, markedly reduced both C3-fragment deposition and MAC formation. Our data suggest that C3-fragment deposition and MAC formation on B lymphocytes in vivo may involve both AP and classical pathway activation, with CR1 contributing significantly to the latter. On the other hand, the presence of extrinsic CR1, on E, may serve to limit spontaneous MAC formation and thereby ensure cell survival in the circulation.
Nielsen
Claus Henrik
CH
Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.
Pedersen
Morten Løbner
ML
Marquart
Hanne Vibeke
HV
Prodinger
Wolfgang Maria
WM
Leslie
Robert Graham Quinton
RG
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival; D015922:Complement C1q / Q000172:deficiency; D003176:Complement C3 / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010446:Peptide Fragments / Q000378:metabolism; D017463:Receptors, Complement 3b / Q000378:metabolism*; D017464:Receptors, Complement 3d / Q000378:metabolism*
D003176:Complement C3; D015938:Complement Membrane Attack Complex; D010446:Peptide Fragments; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D015922:Complement C1q