Regulation of immunoglobulin secretion by factor H of human complement.
As human B lymphocytes and macrophages carry surface receptors for Factor H (B1H), we investigated the possibility that this complement component regulates their function. Factor H inhibits immunoglobulin secretion by peripheral mononuclear cells (MNC) stimulated with pokeweed mitogen if present at the initiation of the cultures and at concentrations greater than 50 micrograms/ml. Factor H also inhibited stimulation and differentiation of purified B cells into immunoglobulin-secreting cells by Epstein-Barr virus (EBV). The inhibitory effect of Factor H was abrogated if anti-Factor H antibody was present in the cultures. EBV-transformed B-cell lines secreted less immunoglobulin if Factor H was present in the culture for at least 4 days. Culture of MNC with Factor H did not lead to the generation of suppressor T cells or macrophages. In contrast, Factor H did not cause proliferation of human peripheral total MNC or enriched T-cell or B-cell subpopulations. Also, Factor H did not inhibit the proliferation of MNC in response to several mitogens and antigens. Our results strongly indicate that Factor H is able to block human B-cell differentiation in vitro without blocking the proliferative ability of the cells. Factor H seems to act directly on the B cells through its receptor on their surface, since it inhibited T-dependent and T-independent B-cell differentiation but generated no suppressor cells.
Tsokos
G C
GC
Inghirami
G
G
Tsoukas
C D
CD
Balow
J E
JE
Lambris
J D
JD
D000921:Antibody-Producing Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002472:Cell Transformation, Viral; D003180:Complement C3b Inactivator Proteins / Q000276:immunology*; D017242:Complement Factor H; D006462:Hemolytic Plaque Technique; D004854:Herpesvirus 4, Human; D006801:Humans; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D011043:Pokeweed Mitogens / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D007136:Immunoglobulins; D011043:Pokeweed Mitogens; D017242:Complement Factor H