CR2 is the primary acceptor site for C3 during alternative pathway activation of complement on human peripheral B lymphocytes.
Human cells infected with certain viruses acquire the ability to activate the alternative pathway (AP) of complement. Complement receptor 2 on EBV-infected lymphoblastoid cell lines has been reported to act as the covalent binding site for C3b during AP activation. Using flow cytometry, we investigated the ability of normal human peripheral blood leukocytes to activate the AP in homologous serum. Deposition of C3 fragments was determined as a measurement of complement activation on each of the subpopulations of the blood cells. Incubating human peripheral blood leukocytes with homologous or autologous serum resulted in C3 deposition on B cells and, to a lesser extent, on monocytes and polymorphonuclear leukocytes. Complement activation in the presence of Mg2+ ions and EGTA revealed major involvement of the AP in the case of B cells, and to a lesser extent for other leukocyte populations examined. Preincubation of the leukocytes with polyclonal anti-complement receptor 2 Ab markedly decreased the C3 fragment deposition, as a result of in vitro AP activation, on B cells, indicating that on normal human B cells this receptor may be involved in AP activation. Freshly isolated, normal human B cells also bear low but significant amounts of C3d,g fragments on their membranes, indicating that this AP activation also occurs in vivo. AP activation was partially decreased in the presence of autologous erythrocytes (RBC) suggesting that complement regulatory proteins on RBC play a role in limiting the AP activation in vivo.
Marquart
H V
HV
Department of Medical Microbiology, Odense University, Denmark.
Svehag
S E
SE
Leslie
R G
RG
D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D018958:CD55 Antigens; D003176:Complement C3 / Q000378:metabolism*; D003170:Complement Pathway, Alternative; D006801:Humans; D066298:In Vitro Techniques; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D017463:Receptors, Complement 3b / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000378:metabolism*
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D003176:Complement C3; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d