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Selective dysregulation of the FcIIB receptor on memory B cells in SLE

¹ Department of Medicine, Columbia University Medical Center, New York, NY 10032
² Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
³ MacroGenics Inc., Rockville, MD 20850
⁴ The Rockefeller University, New York, NY 10021

CORRESPONDENCE Meggan Mackay: mcm2123{at}columbia.edu

The inappropriate expansion and activation of autoreactive memory B cells and plasmablasts contributes to loss of self-tolerance in systemic lupus erythematosus (SLE). Defects in the inhibitory Fc receptor, FcRIIB, have been shown to contribute to B cell activation and autoimmunity in several mouse models of SLE. In this paper, we demonstrate that expression of FcRIIB is routinely up-regulated on memory B cells in the peripheral blood of healthy controls, whereas up-regulation of FcRIIB is considerably decreased in memory B cells of SLE patients. This directly correlates with decreased FcRIIB-mediated suppression of B cell receptor–induced calcium (Ca²⁺) response in those B cells. We also found substantial overrepresentation of African-American patients among those who failed to up-regulate FcRIIB. These results suggest that the inhibitory receptor, FcRIIB, may be impaired at a critical checkpoint in SLE in the regulation of memory B cells; thus, FcRIIB represents a novel target for therapeutic interventions in this disease.

Abbreviations used: BCR, B cell receptor; CHO, Chinese hamster ovary; dsDNA, double-stranded DNA; FcR, Fc receptor; MFI, mean fluorescence intensity; SLE, systemic lupus erythematosus; SLEDAI, SLE disease activity index.

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