Fc gammaRIIb inhibits both B cell receptor- and CD19-induced Ca2+ mobilization in Fc gammaR-transfected human B cells.
Fc gammaRIIb inhibits both B cell receptor- and CD19-induced Ca2+ mobilization in Fc gammaR-transfected human B cells.
复制标题
Fc gammaRIIb 抑制 Fc gammaR 转染的人 B 细胞中 B 细胞受体和 CD19 诱导的 Ca2 动员。
作者：
G. Koncz;J. Gergely;G. Sármay
Fc γ RIIb（CD 32）在体内与B细胞抗原受体（BCR）共簇集时，通过由分泌的IgG和抗原组成的免疫复合物下调细胞活化来控制抗体产生。体外Fc γ RIIb-BCR共连接显示抑制细胞外间隙的Ca 2+内流，其机制尚未完全理解。人B细胞表达Fc γ RIIb 1和Fc γ RIIb 2，不同之处仅在于前者胞质尾中的19个氨基酸长的插入物。为了阐明Fc γ RIIb 1和Fc γ RIIb 2亚型在B细胞的下调中是否显示任何差异，我们研究了BCR和Fc γ RIIb 1或Fc γ RIIb 2的共聚集对Burkitt淋巴瘤细胞系ST 486中Ca 2+信号传导的影响，ST 486分别用两种亚型转染。我们在此首次表明，BCR和Fc γ RIIb的共聚集也可抑制人B细胞内质网池的Ca 2+释放。两种亚型均介导这种抑制作用，抑制作用取决于BCR与Fc γ RIIb交联的比例。与Fc γ RIIb相反，CD 21/CD 19复合物显示通过降低活化阈值上调B细胞应答。我们在此已经表明，Fc γ RIIb与CD 19的共聚簇抑制了CD 19诱导的Ca 2+内流。此外，与BCR-加CD 19诱导的Ca 2+反应相比，Fc γ RIIb与BCR和CD 19的三方共聚集导致Ca 2+反应降低，表明Fc γ RIIb可能抑制CD 19诱导的B细胞活化增强。在这些数据的基础上，我们认为，IgG和C3 d固定免疫复合物可能会下调B细胞的反应，通过干扰BCR和CD 19介导的Ca 2+动员。
Fc gammaRIIb (CD32) controls antibody production by down-regulating cell activation, when co-clustered with B cell antigen receptors (BCR) in vivo, via immune complexes consisting of secreted IgG and antigen. Fc gammaRIIb-BCR co-ligation in vitro was shown to inhibit the Ca2+ influx from the extracellular space, the mechanism of which is not fully understood. Human B cells express Fc gammaRIIb1 and Fc gammaRIIb2, differing only in a 19 amino acid long insert in the cytoplasmic tail of the former. To elucidate whether Fc gammaRIIb1 and Fc gammaRIIb2 isoforms show any difference in the down-regulation of B cells, we have studied the effect of co-clustering of BCR and Fc gammaRIIb1 or Fc gammaRIIb2 on the Ca2+ signaling in a Burkitt's lymphoma cell line, ST486, transfected with the two isoforms respectively. We have shown here, for the first time, that co-aggregation of BCR and Fc gammaRIIb may also inhibit Ca2+ release from the endoplasmic reticulum pool of human B cells. Both isoforms mediated this inhibition and the inhibitory effect depended on the ratio of BCR to Fc gammaRIIb cross-linking. In contrast to Fc gammaRIIb, the CD21/CD19 complex was shown to up-regulate B cell response by lowering the activation threshold. We have shown here that co-clustering of Fc gammaRIIb with CD19 inhibited the CD19-induced Ca2+ influx. Furthermore, the three party co-aggregation of Fc gammaRIIb with BCR and CD19 resulted in a decreased Ca2+ response, as compared to the BCR- plus CD19-induced one, indicating that Fc gammaRIIb may inhibit CD19-induced enhancement of B cell activation. On the basis of these data we suggest that IgG-containing and C3d-fixing immune complexes may down-regulate the B cell response by interfering with both BCR- and CD19-mediated Ca2+ mobilization.
影响因子：
56.9
作者：
CARTER, RH;FEARON, DT
通讯作者：
FEARON, DT
影响因子：
56.9
作者：
TUVESON, DA;CARTER, RH;FEARON, DT
通讯作者：
FEARON, DT
B 细胞中的负信号传导通过减少 Shc-Grb2 相互作用而导致 Ras 活性降低。
DOI：
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发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Tridandapani,S;Chacko,GW;VanBrocklyn,JR;Coggeshall,KM
通讯作者：
Coggeshall,KM