Clark M R, Friedrich R J, Campbell K S, Cambier J C
National Jewish Center for Immunology and Respiratory Medicine, Department of Pediatrics, Denver, CO 80206.
J Immunol. 1992 Nov 1;149(9):2857-63.
B cell activation after Ag binding to membrane Ig (mIg) is mediated by a complex series of events that involves proximal activation of a tyrosine kinase and phospholipase C. Until recently it was unclear how mIgM and mIgD, with their limited cytoplasmic domains (three amino acids on each H chain), were able to couple to these secondary signal transducers. Studies of murine B cells conducted in several laboratories, including our own, suggest that products of the mb-1 (IgM-alpha or IgD-alpha) and B29 (Ig-beta, Ig-gamma) genes occur as disulfide-linked alpha/beta and alpha/gamma heterodimers that are noncovalently associated with mIgM and mIgD. Although studies utilizing Daudi and Raji cell lines indicate that human mIgM is also associated with a dimer containing the mb-1 gene product, the other molecules associated with the human receptor have not been identified. In this report we characterize the phosphoproteins that are noncovalently associated with mIgM on human tonsillar B cells and human pre-B cell lines. mIgM is noncovalently associated with a disulfide-linked heterodimer composed of variably glycosylated forms of two core proteins with apparent molecular mass of 26.5 and 27 kDa. Western blotting analysis reveals that the lower m.w. component of each of the mIgM-associated heterodimers and its 27-kDa deglycosylated core protein are reactive with antibodies against the murine B29 gene product. Thus, a product of the B29 gene is a component of the AgR complex in human and murine B cells, occurring as a disulfide linked dimer with product(s) of the mb-1 gene. Interestingly, mb-1 and B29 gene products expressed on human cells are much more heterogenously N-glycosylated than their murine B cell counterparts.
抗原与膜免疫球蛋白（mIg）结合后，B细胞的激活是由一系列复杂事件介导的，这些事件涉及酪氨酸激酶和磷脂酶C的近端激活。直到最近，还不清楚mIgM和mIgD因其有限的胞质结构域（每条重链上有三个氨基酸）如何能够与这些二级信号转导分子偶联。包括我们自己实验室在内的几个实验室对小鼠B细胞进行的研究表明，mb-1（IgM-α或IgD-α）和B29（Ig-β、Ig-γ）基因的产物以二硫键连接的α/β和α/γ异二聚体形式存在，它们与mIgM和mIgD非共价结合。尽管利用Daudi和Raji细胞系的研究表明人mIgM也与含有mb-1基因产物的二聚体相关，但与人类受体相关的其他分子尚未确定。在本报告中，我们对人扁桃体B细胞和人前B细胞系上与mIgM非共价结合的磷蛋白进行了表征。mIgM与一个二硫键连接的异二聚体非共价结合，该异二聚体由两种核心蛋白的可变糖基化形式组成，表观分子量分别为26.5 kDa和27 kDa。蛋白质印迹分析显示，每个与mIgM相关的异二聚体的低分子量组分及其27 kDa的去糖基化核心蛋白与抗小鼠B29基因产物的抗体发生反应。因此，B29基因的产物是人和小鼠B细胞中抗原受体复合物的一个组分，它与mb-1基因的产物以二硫键连接的二聚体形式存在。有趣的是，在人类细胞上表达的mb-1和B29基因产物的N-糖基化比其小鼠B细胞对应物更加不均一。
