Complement receptor type 1 (CR1, CD35) is a potent inhibitor of B-cell functions in rheumatoid arthritis petients

Kremlitzka, Mariann and Polgár, Anna and Fülöp L., Lívia and Kiss, Emese and Poór, Gyula and Erdei, Anna (2013) Complement receptor type 1 (CR1, CD35) is a potent inhibitor of B-cell functions in rheumatoid arthritis petients. INTERNATIONAL IMMUNOLOGY, 25 (1). pp. 25-33. ISSN 0953-8178

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Abstract

The involvement of B cells, complement activation and subsequent immune complex deposition has all been implicated in the pathogenesis of rheumatoid arthritis (RA). While the reduced expression of complement receptor 1 (CR1, CD35) and 2 (CR2, CD21) on the B cells of RA patients is known for long, their exact role in B cell tolerance and autoimmunity is not yet fully understood. To get a deeper insight into the possible mechanisms we studied the expression and function of CR1 and CR2 on various subsets of B cells of healthy donors and RA patients at various stages of the disease by FACS analysis, H3-thymidine incorporation and ELISA. We found, that CD19+CD27- naive B cells up-regulate the expression of the inhibitory CR1 during differentiation to CD19+CD27+ memory B cells both in healthy donors and in RA patients, while the expression of the activatory CR2 is down-regulated. This clearly demonstrates that the expression of these two antagonistic complement receptors is regulated differentially during the development of human B cells, a phenomenon which may influence the maintenance of peripheral B cell tolerance. Our functional studies show that after clustering CR1 both by its natural ligand and To5 mAb, the inhibitory function of CD35 is maintained in RA patients, despite its significantly reduced expression compared to healthy individuals. Besides blocking BCR-induced proliferation, CR1 inhibits the differentiation of B cells to plasmablasts and their Ig-production. Since the reduced expression of CR1 in RA patients does not affect its inhibitory function, this receptor might serve as a new target for therapeutical interventions.

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