Functions of SWAP-70 in B Cell Activation

描述(申请人提供)：SWAP-70在B-CELL中的功能 激活B淋巴细胞和诱导核的激活信号通路 免疫球蛋白(Ig)重链类转换、DNA修复和 人们对DNA复制的了解还不完全。我们已经确定并 鉴定了一种新的磷酸蛋白SWAP-70，该蛋白是特异性表达的 在激活的B细胞和肥大细胞中。SWAP-70具有信号传递的特征 蛋白质在细胞质和细胞核之间转位，与DNA修复相互作用 细胞核中的蛋白质，并与B细胞抗原受体相关。我们的 一只SWAP70-/-缺陷小鼠的初步分析表明需要 对于CD4O触发的增殖和Ig类转换中的SWAP-70，以及对于 伽玛射线照射后存活。因此，这其中的中心假设 应用提示B细胞中蛋白SWAP-70的重要贡献 激活。这个应用程序的具体目标是理解角色 SWAP-70在细胞增殖、Ig类转换、DNA修复和细胞凋亡中的作用 B细胞。B细胞的激活是免疫反应的关键，如果不恰当的话 被控制，是几种人类免疫系统疾病的核心。因此， 分析SWAP-70在B细胞激活中的作用可能有助于我们 了解正常的B细胞功能以及免疫缺陷， B细胞恶性肿瘤、自身免疫和过敏。

DESCRIPTION (Provided by the Applicant): Functions of SWAP-70 in B-cell Activation Signaling pathways that activate B lymphocytes and induce nuclear processes like immunoglobulin (Ig) heavy chain class switching, DNA repair, and DNA replication are incompletely understood. We have identified and characterized a novel phosphoprotein, SWAP-70, that is specifically expressed in activated B-cells and in mast cells. SWAP-70 has hallmarks of signaling proteins, translocates between cytoplasm and nucleus, interacts with DNA repair proteins in the nucleus, and associates with the B-cell antigen receptor. Our preliminary analysis of a mouse deficient in SWAP70-/- indicates a requirement for SWAP-70 in CD4O-triggered proliferation and Ig class switching, and for survival after gamma-irradiation. Thus, the central hypothesis in this application suggests an important contribution by protein SWAP-70 in B-cell activation. The specific aims of this application are to understand the roles of SWAP-70 in proliferation, Ig class switching, DNA repair, and apoptosis in B-cells. B-cell activation is key to the immune response and, if improperly controlled, at the heart of several human immune system diseases. Therefore, the analysis of SWAP-70 in B-cell activation is likely to help in our understanding of normal B-cell function as well as of immune deficiencies, B-cell malignancies, autoimmunity, and allergy.