Lazarus A H, Mills G B, Crow A R, Delovitch T L
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
J Immunol. 1991 Sep 15;147(6):1739-45.
The interaction of an Ag ligand with its B cell surface Ig (sIg) receptor can occur via an FcR-dependent or -independent pathway. We previously found that transfected TNP-specific B cells undergo both Ca2+ signaling and desensitization upon interaction with the thymus-dependent Ag TNP-OVA. Similarly, we showed that these B cells can also be desensitized by cross-linking sIg to the Fc gamma R via the formation of an Ag-antibody bridge. Thus, Ag-specific B cells can be desensitized by two different Ag-dependent events, one mediated by Ag-sIg interaction and the other by sIg-Fc gamma R cross-linking. Inasmuch as Ag-sIg and sIg-Fc gamma R interactions lead to positive and negative signaling, it was of interest to determine whether B cell desensitization mediated by these interactions occurs by one of the well known signaling pathways in B cells. We found that Ag-induced changes in [Ca2+]i could be readily dissociated from Ag-induced desensitization, indicating that a Ca(2+)-independent pathway is likely responsible for this pathway of desensitization. To determine if PKC plays a role in B cell desensitization mediated by either Ag or sIg-Fc gamma R interaction, PKC was downregulated by long term exposure to 12-O-tetradecanoylphorbol 13-acetate or inhibited by exposure of cells to staurosporine. The PKC down-regulated and inhibited cells underwent similar Ag- and Fc gamma R-dependent desensitization compared to cells containing active PKC. Taken together, these data indicate that Ag-induced desensitization of B cell signaling likely involves an event(s) that occurs either upstream or independent of Ag-induced elevations in [Ca2+]i and PKC activation.
抗原（Ag）配体与其B细胞表面免疫球蛋白（sIg）受体的相互作用可通过Fc受体依赖或非依赖途径发生。我们之前发现，转染的三硝基苯（TNP）特异性B细胞在与胸腺依赖性抗原TNP-卵清蛋白（OVA）相互作用时会经历钙离子（Ca2+）信号传导和脱敏过程。同样，我们表明这些B细胞也可通过形成抗原-抗体桥将sIg与FcγR交联而实现脱敏。因此，抗原特异性B细胞可通过两种不同的抗原依赖性事件实现脱敏，一种由抗原-sIg相互作用介导，另一种由sIg-FcγR交联介导。鉴于抗原-sIg和sIg-FcγR相互作用会导致正向和负向信号传导，确定由这些相互作用介导的B细胞脱敏是否通过B细胞中一种众所周知的信号传导途径发生就很有意义。我们发现，抗原诱导的细胞内钙离子浓度（[Ca2+]i）变化很容易与抗原诱导的脱敏过程分离，这表明一种不依赖钙离子（Ca2+）的途径可能是这种脱敏途径的原因。为了确定蛋白激酶C（PKC）是否在由抗原或sIg-FcγR相互作用介导的B细胞脱敏中发挥作用，通过长期暴露于12-O-十四烷酰佛波醇13-乙酸酯使PKC下调，或通过使细胞暴露于星形孢菌素对其进行抑制。与含有活性PKC的细胞相比，PKC下调和受抑制的细胞经历了类似的抗原和FcγR依赖性脱敏。综上所述，这些数据表明，抗原诱导的B细胞信号脱敏可能涉及发生在抗原诱导的[Ca2+]i升高和PKC激活上游或与之无关的一个或多个事件。
