Defective FcgammaRIIb1 signaling contributes to enhanced calcium response in B cells from patients with systemic lupus erythematosus.

B lymphocytes from patients with systemic lupus erythematosus (SLE) display enhanced B cell antigen receptor (BCR)-mediated early signal transduction events, including increased fluxes of intracytoplasmic calcium ([Ca(2+)](i)). Because crosslinking of FcgammaRIIb1 (CD32) in normal B cells suppresses the BCR-initiated signal transduction process, we investigated whether the increased BCR-initiated [Ca(2+)](i) response in SLE B cells is the consequence of decreased FcgammaRIIb1-mediated suppression. To this end, we used flow cytometry to study the [Ca(2+)](i) responses of indo-1-loaded negatively gated B cells stimulated with F(ab')(2) fragments or whole IgG anti-human micro Ab. We found that the ratio of F(ab')(2) to whole anti-micro Ab [Ca(2+)](i) response was significantly lower in SLE B cells compared to B cells from patients with other systemic rheumatic diseases or normal individuals (P < 0.01). Because the surface expressions of FcgammaRIIb1 and surface IgM were similar in B cells from SLE patients and disease and normal controls, these data indicate a decrease in FcgammaRIIb-mediated suppression in SLE B cells. In addition, the whole IgG anti-micro Ab but not its F(ab')(2) fragment caused increased redistribution of SH2 domain-containing inositol 5'phosphatase in SLE compared to normal and disease control B cells. In conclusion, deficient FcgammaRIIb1-mediated suppression contributes to the augmented [Ca(2+)](i) responses of human SLE B cells. Copyright 2001 Academic Press.