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The Journal of Immunology, 2002, 168: 2782-2788.
Copyright © 2002 by The American Association of Immunologists

Complement Receptor Type 1 (CD35) Mediates Inhibitory Signals in Human B Lymphocytes1

Mihály Józsi*, József Prechl*,{dagger}, Zsuzsa Bajtay*,{dagger} and Anna Erdei2,*,{dagger}

* Department of Immunology and {dagger} Research Group of the Hungarian Academy of Sciences, Eötvös Loránd University, Budapest, Hungary

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(H2O), 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 Ca2+ 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.




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