Expression and function of B cell specific MB-1 protein associated with IgM receptor

B细胞抗原受体是由抗原特异性膜IgM分子及其相关蛋白MB-1(Ig-α，CD79a)和B29(Ig-β，CD79b)组成，这种基本结构不仅对B细胞表面抗原受体的表达是必需的，而且对抗原提供的刺激信号的信号转导也是必不可少的。在MB-1和B29的胞质结构域中，存在抗原识别共识基序，可以与信号转导相关的各种功能成分结合。B细胞抗原受体复合体包括src-型酪氨酸激酶Lyn、Fyn、Lck、Blk、非src-tyupe酪氨酸激酶Syk和PI-3激酶。抗原受体的交联会诱导磷脂酰肌醇途径的信号转导，导致细胞内钙动员和蛋白激酶活性的增加。它还诱导ras-Meck/MAPK通路的信号转导，导致核转录因子的激活。对B细胞表面抗原受体的激活也会诱导PI-3激酶活性，从而可能为B细胞的增殖和分化提供重要的信号。除了这些关于B细胞信号转导途径的基本发现外，人们对这些信号转导途径在B细胞不同阶段的信号转导的机制和质量知之甚少。为了明确识别与B细胞抗原受体复合体相关的新分子，我们寻找了与MB-1蛋白相关的功能性磷蛋白分子。抗MB-1蛋白与52 kDa蛋白共沉淀。我们制备了大鼠抗该52 kDa蛋白的单抗，并用该单抗分离了一个候选的c DNA克隆，命名为α4。Alpha4基因克隆是一种与B细胞中的蛋白激酶分子紧密结合的新分子，位于B细胞抗原受体信号转导的下游。

B cell antigent receptor is composed of antigen specific membrane IgM molecule and its associated proteins of MB-1 (Ig-alpha, CD79a) and B29 (Ig-beta, CD79b) .This basic structure is essential not only for the expression of B cell antigen receptor on the surface of B lymphocytes but also for signal transduction of stimulatory signal given by antigen. Within cytoplasmic domains of MB-1 and B29, there are antigen recognition consensus motif that can bind to various functional components related to the signal transduction. B cell antigen receptor complex involves src-type tyrosine kinase Lyn, Fyn, Lck, Blk, non src-tyupe tyrosine kinase Syk, and PI-3 kinase. Crosslinking of antigen receptor induces signal transduction of phosphatidyl inositol patyways, leading to the increase of intracellular Ca mobilization and protein kinase sctivity. It also induces signal transduction of ras-MECK/MAPK pathway leading to activation of nuclear transcription factors. Activation to antigen receptor on B cells also induces PI-3 kinase activity which then probably mediates important signal for the proliferation and differentiation of B cells.Regardless of these fundamental findings concerning to B cell signal transduction pathways, little is known about the mechanism and quality of signal transduction through these signal transduction pathways in different stages of B lineage cells. To clearly identify novel molecules involved in the B cell antigen receptor complex, we searched for the functional phosphoprotein molecules associated with MB-1 protein. A 52 kDa protein is coprecipitated with anti-MB-1 protein. We prepared rat monoclonal antibody against this 52 kDa protein and isolated a candidate cDNA clone named alpha4 with this monoclonal antibody. The alpha4 cDNA clone is a new molecule which is tightly associated with kinase molecules in B cells, which is located in the down stream of the signal transduction through B cell antigen raceptor.