Regulation of auto-reactive B cell activation by Ras signaling pathway

点击翻译按钮获取中文摘要

In this study we are succeeded in the generation of RasGRP3-deficient mice. We found that BCR-mediated Ras activation is impaired in RasGRP3-deficient B cAls and that activation of Ras in B cells are mainly due to the activation of RasGRP3, which is in contrast with some of the previous reports which suggested activation of Ras is mediated by SOS pathway. Serum anti-DNAantilicdy titer was significantly higher than the control suggesting that selection of autoreactive B cells might be impaired. In order to confirm this issue, we crossed the mice with anti-BEL Ig transgenic mice and transferred the B cells into sBEL expressing recipient mice. As the result we found that transferred B cells are not completely deleted suggesting that apoptosis in RasGRP3-deficientB cells are impaired.To further analyze this issue, mitochondorial membrane potential, which is crucial for the regulation of apoptosis, was examined after strong ligation of surface BCR, which is one of the stimuli known to induce apopotosis. As the result, we found that mitochondorial membrane potential was disregulated at the early time point after the cross-ligation. Further, we found that activation of bc1-2 was impaired in RasGRP3-deficient B cells, which might be one of the reason which can explain the impaired apoptosis in RasGRP3-deficient B cells.