Selective dysregulation of the FcgammaIIB receptor on memory B cells in SLE.
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, FcgammaRIIB, 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 FcgammaRIIB is routinely up-regulated on memory B cells in the peripheral blood of healthy controls, whereas up-regulation of FcgammaRIIB is considerably decreased in memory B cells of SLE patients. This directly correlates with decreased FcgammaRIIB-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 FcgammaRIIB. These results suggest that the inhibitory receptor, FcgammaRIIB, may be impaired at a critical checkpoint in SLE in the regulation of memory B cells; thus, FcgammaRIIB represents a novel target for therapeutic interventions in this disease.
Mackay
Meggan
M
Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA. mcm2123@columbia.edu
Stanevsky
Anfisa
A
Wang
Tao
T
Aranow
Cynthia
C
Li
Margaret
M
Koenig
Scott
S
Ravetch
Jeffrey V
JV
Diamond
Betty
B
D000328:Adult; D001741:Black or African American; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism*
C499173:FCGR2B protein, human; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D002118:Calcium