Complement receptor type 1 (CD35) mediates inhibitory signals in human B lymphocytes.
The complement system---particularly component C3---has been demonstrated to be a key link between innate and adaptive immunity. The trimolecular complex of complement receptor type 2 (CR2), CD19, and CD81 is known to promote B cell activation when coligated with the B cell Ag receptor. In the present study, we aimed to elucidate the role of human complement receptor type 1 (CR1), the other C3-receptor on B cells. As ligand, aggregated C3 and aggregated C3(H(2)O), i.e., multimeric "C3b-like C3", are used, which bind to CR1, but not to CR2. In experiments studying the functional consequences of CR1-clustering, the multimeric ligand is shown to inhibit the proliferation of tonsil B cells activated with a suboptimal dose of anti-IgM F(ab')(2). Importantly, this inhibitory activity also occurs in the presence of the costimulatory cytokines IL-2 and IL-15. The anti-IgM-induced transient increase in the concentration of intracellular free Ca(2+) and phosphorylation of several cytoplasmic proteins are strongly reduced in the presence of the CR1 ligand. Data presented indicate that CR1 has a negative regulatory role in the B cell Ag receptor mediated activation of human B lymphocytes.
Józsi
Mihály
M
Department of Immunology and Research Group of the Hungarian Academy of Sciences, Eötvös Loránd University, Budapest, Hungary.
Prechl
József
J
Bajtay
Zsuzsa
Z
Erdei
Anna
A
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002648:Child; D003176:Complement C3 / Q000378:metabolism / Q000494:pharmacology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D006131:Growth Inhibitors / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D019409:Interleukin-15 / Q000037:antagonists & inhibitors / Q000502:physiology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D010766:Phosphorylation; D011485:Protein Binding / Q000276:immunology; D017463:Receptors, Complement 3b / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D003176:Complement C3; D018985:Epitopes, B-Lymphocyte; D006131:Growth Inhibitors; D007075:Immunoglobulin M; D019409:Interleukin-15; D007376:Interleukin-2; D017463:Receptors, Complement 3b; C044203:anti-IgM; D014443:Tyrosine; D002118:Calcium