Koncz G, Gergely J, Sármay G
Department of Immunology, Loránd Eötvös University, Göd, Hungary.
Int Immunol. 1998 Feb;10(2):141-6. doi: 10.1093/intimm/10.2.141.
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.
FcγRIIb（CD32）通过在体内与B细胞抗原受体（BCR）共聚集时，经由分泌型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。体外实验表明，FcγRIIb-BCR共连接可抑制细胞外空间的Ca2+内流，但其机制尚未完全明确。人类B细胞表达FcγRIIb1和FcγRIIb2，二者仅在前体细胞质尾中存在一个19个氨基酸长的插入片段上有所不同。为阐明FcγRIIb1和FcγRIIb2亚型在B细胞下调方面是否存在差异，我们分别研究了在转染了这两种亚型的伯基特淋巴瘤细胞系ST486中，BCR与FcγRIIb1或FcγRIIb2共聚集对Ca2+信号传导的影响。我们首次在此表明，BCR与FcγRIIb的共聚集也可能抑制人类B细胞内质网池中的Ca2+释放。两种亚型均介导了这种抑制作用，且抑制效果取决于BCR与FcγRIIb交联的比例。与FcγRIIb相反，CD21/CD19复合物通过降低活化阈值来上调B细胞反应。我们在此表明，FcγRIIb与CD19的共聚集抑制了CD19诱导的Ca2+内流。此外，与BCR加CD19诱导的情况相比，FcγRIIb与BCR和CD19的三方共聚集导致Ca2+反应降低，表明FcγRIIb可能抑制CD19诱导的B细胞活化增强。基于这些数据，我们认为含IgG和结合C3d的免疫复合物可能通过干扰BCR和CD19介导的Ca2+动员来下调B细胞反应。
