Defective FcγRIIb1 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 ([Ca2+]i). Because crosslinking of FcγRIIb1 (CD32) in normal B cells suppresses the BCR-initiated signal transduction process, we investigated whether the increased BCR-initiated [Ca2+]i response in SLE B cells is the consequence of decreased FcγRIIb1-mediated suppression. To this end, we used flow cytometry to study the [Ca2+]i responses of indo-1-loaded negatively gated B cells stimulated with F(ab′)2 fragments or whole IgG anti-human μ Ab. We found that the ratio of F(ab′)2 to whole anti-μ Ab [Ca2+]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 FcγRIIb1 and surface IgM were similar in B cells from SLE patients and disease and normal controls, these data indicate a decrease in FcγRIIb-mediated suppression in SLE B cells. In addition, the whole IgG anti-μ 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 FcγRIIb1-mediated suppression contributes to the augmented [Ca2+]i responses of human SLE B cells.