Modulation of the C3 Receptor by HLA Antibodies and C1, 4, 2, and 3 Components of Complement

Abstract

Abstract Recent studies have suggested linkage of genes regulating synthesis of C2 and genes of the MHC complex with M.S. and certain autoimmune diseases. As Ig-secreting plasma cells are related ontogenically to a subpopulation of B lymphocytes which selectively express the C3 receptor, these findings suggest linkage of C2, CRL cells and membrane products of MHC genes, with pathogenic mechanisms mediating diseases of humoral immunity. The following studies were initiated to determine whether a functional relationship could be demonstrated between antibodies to membrane products of MHC genes, the activation unit of the classical complement pathway and C3 receptors. Monospecific HLA-A2 antibody and functionally pure human C1, C4, and C2 were used to initiate the assembly of C3 convertase on membranes of enriched populations of human B lymphocytes. The sensitized lymphocytes were then incubated with EAC1-3 cellular intermediates and formation of C3 rosettes was determined. Formation of C3 rosettes with the sensitized lymphocytes was reduced by over 50% from values obtained with unsensitized controls.