PMID: 11899427Mar 20, 2002Paper

CR2-mediated activation of the complement alternative pathway results in formation of membrane attack complexes on human B lymphocytes

Immunology
C H NielsenR G Leslie

Abstract

Normal human B lymphocytes activate the alternative pathway of complement via complement receptor type 2 (CR2, CD21), that binds hydrolysed C3 (iC3) and thereby promotes the formation of a membrane-bound C3 convertase. We have investigated whether this might lead to the generation of a C5 convertase and consequent formation of membrane attack complexes (MAC). Deposition of C3 fragments and MAC was assessed on human peripheral B lymphocytes in the presence of 30% autologous serum containing 4.4 mM MgCl2/20 mM EGTA, which abrogates the classical pathway of complement without affecting the alternative pathway. Blockade of the CR2 ligand-binding site with the monoclonal antibody FE8 resulted in 56 +/- 13% and 71 +/- 9% inhibition of the C3-fragment and MAC deposition, respectively, whereas the monoclonal antibody HB135, directed against an irrelevant CR2 epitope, had no effect. Blockade of the CR1 binding site with the monoclonal antibody 3D9 also resulted in a minor reduction in MAC deposition, while FE8 and 3D9, in combination, markedly reduced deposition of both C3 fragments (91 +/- 5%) and C9 (95 +/- 3%). The kinetics of C3-fragment and MAC deposition, as well as the dependence of both processes on CR2, indicate that MAC format...Continue Reading

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Citations

Apr 24, 2010·Transplant International : Official Journal of the European Society for Organ Transplantation·Takafumi MachimotoJuan Scornik
Sep 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cody A KochJeffrey L Platt
Mar 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amanda C JacobsonJohn H Weis
Aug 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sherry D FlemingV Michael Holers

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