Enyedy E J, Mitchell J P, Nambiar M P, Tsokos G C
Department of Cellular Injury, Walter Reed Army Institute of Research, Building 503, Robert Grant Avenue, Silver Spring, MD 20910-7500, USA.
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+)). 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+) 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+) 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+) 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+) responses of human SLE B cells.
系统性红斑狼疮（SLE）患者的B淋巴细胞表现出增强的B细胞抗原受体（BCR）介导的早期信号转导事件，包括胞浆内钙（[Ca(2+)]i）通量增加。由于正常B细胞中FcγRIIb1（CD32）的交联会抑制BCR启动的信号转导过程，我们研究了SLE B细胞中BCR启动的[Ca(2+)]i反应增加是否是FcγRIIb1介导的抑制作用降低的结果。为此，我们使用流式细胞术研究了用F(ab')(2)片段或全IgG抗人μ抗体刺激的indo-1负载的阴性门控B细胞的[Ca(2+)]i反应。我们发现，与其他系统性风湿性疾病患者或正常个体的B细胞相比，SLE B细胞中F(ab')(2)与全抗μ抗体[Ca(2+)]i反应的比率显著降低（P < 0.01）。由于SLE患者、疾病和正常对照的B细胞中FcγRIIb1和表面IgM的表面表达相似，这些数据表明SLE B细胞中FcγRIIb介导的抑制作用降低。此外，与正常和疾病对照B细胞相比，全IgG抗μ抗体而非其F(ab')(2)片段导致SLE中含SH2结构域的肌醇5'磷酸酶的重新分布增加。总之，FcγRIIb1介导的抑制作用不足导致人类SLE B细胞的[Ca(2+)]i反应增强。
