Rudge Elizabeth U, Cutler Antony J, Pritchard Nicholas R, Smith Kenneth G C
Cambridge Institute for Medical Research and the Department of Medicine, Wellcome Trust/MRC Building, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom.
J Exp Med. 2002 Apr 15;195(8):1079-85. doi: 10.1084/jem.20011435.
Inhibitory receptors CD22, Fc gamma RII (CD32), CD72, and paired immunoglobulin-like receptor (PIR)-B are critically involved in negatively regulating the B cell immune response and in preventing autoimmunity. Here we show that interleukin 4 (IL-4) reduces expression of all four on activated B cells at the level of messenger RNA and protein. This reduced expression is dependent on continuous exposure to IL-4 and is mediated through Stat6. Coligation of Fc gamma RII to the B cell receptor (BCR) via intact IgG increases the B cell activation threshold and suppresses antigen presentation. IL-4 completely abolishes these negative regulatory effects of Fc gamma RII. CD22 coligation with the BCR also suppresses activation -- this suppression too is abolished by IL-4. Thus, IL-4 is likely to enhance the B cell immune response by releasing B cells from inhibitory receptor suppression. By this coordinate reduction in expression of inhibitory receptors, and release from CD22 and Fc gamma RII-mediated inhibition, IL-4 is likely to play a role in T cell help of B cells and the development of T helper cell type 2 responses. Conversely, B cell activation in the absence of IL-4 would be more difficult to achieve, contributing to the maintenance of B cell tolerance in the absence of T cell help.
抑制性受体CD22、FcγRII（CD32）、CD72和配对免疫球蛋白样受体（PIR）-B在负向调节B细胞免疫应答及预防自身免疫方面起着关键作用。在此我们表明，白细胞介素4（IL-4）在信使核糖核酸和蛋白质水平降低活化B细胞上所有这四种受体的表达。这种表达降低依赖于持续暴露于IL-4，并通过信号转导和转录激活因子6（Stat6）介导。通过完整的免疫球蛋白G（IgG）使FcγRII与B细胞受体（BCR）共连接可提高B细胞活化阈值并抑制抗原呈递。IL-4完全消除了FcγRII的这些负向调节作用。CD22与BCR共连接也会抑制活化——这种抑制同样被IL-4消除。因此，IL-4可能通过解除抑制性受体的抑制作用来增强B细胞免疫应答。通过这种对抑制性受体表达的协同下调以及从CD22和FcγRII介导的抑制作用中释放出来，IL-4可能在B细胞的T细胞辅助及2型辅助性T细胞应答的发展中发挥作用。相反，在没有IL-4的情况下B细胞活化将更难实现，这有助于在没有T细胞辅助时维持B细胞耐受性。
