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

Clin Immunol. 2001 Nov;101(2):130-5. doi: 10.1006/clim.2001.5104.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / metabolism*
  • Calcium Signaling*
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Middle Aged
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
  • Phosphoric Monoester Hydrolases / physiology
  • Receptors, Antigen, B-Cell / physiology
  • Receptors, IgG / physiology*


  • Immunoglobulin G
  • Immunoglobulin M
  • Receptors, Antigen, B-Cell
  • Receptors, IgG
  • Phosphoric Monoester Hydrolases
  • INPPL1 protein, human
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases