CR2-mediated activation of the complement alternative pathway results in formation of membrane attack complexes on human B lymphocytes
| Autor: | W. M. Prodinger, Robert Graham Quinton Leslie, Claus Henrik Nielsen, Hanne V. Marquart |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
B-Lymphocytes
medicine.drug_class Chemistry Immunology Complement Pathway Alternative Complement receptor Complement Membrane Attack Complex Original Articles Monoclonal antibody Complement C9 Molecular biology Epitope C3-convertase C5-convertase Classical complement pathway Biochemistry Complement C3d medicine Alternative complement pathway Receptors Complement 3b Immunology and Allergy Humans Receptors Complement 3d Complement membrane attack complex Cells Cultured |
| Zdroj: | Immunology. 104(4) |
| ISSN: | 0019-2805 |
| Popis: | Summary 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 formation is a consequence of alternative pathway activation. |
| Databáze: | OpenAIRE |
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