Nakamura T, Kubagawa H, Cooper M D
Department of Medicine, University of Alabama, Birmingham.
Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8522-6. doi: 10.1073/pnas.89.18.8522.
Two covalently linked transmembrane molecules, encoded in mice by the mb-1 and B29 genes, have been defined as integral components of the antibody receptor units expressed on B cells. We have produced monoclonal antibodies against an exposed extracellular epitope on the putative human equivalent of the mouse B29 product. These antibodies, CB3-1 and -2, were used to show that cytoplasmic expression of this molecule begins in human pro-B cells (terminal deoxynucleotidyltransferase-positive, mu chain-negative), whereas surface expression coincides strictly with surface immunoglobulin expression of all isotypes. Immunochemical analysis of the human immunoglobulin-associated molecules revealed greater molecular heterogeneity than has been noted for the murine analogues. This molecular heterogeneity of immunoglobulin-associated molecules varied as a function of differentiation stage and the immunoglobulin isotypes expressed by B-lineage cells. Our data support the hypothesis that biochemical heterogeneity of the surface immunoglobulin-associated molecules may contribute to the variability in biological effects of antigen receptor crosslinkage on B cells of different maturational stages. Because the CB3 antibodies are capable of down-modulating the antigen receptors on all B cells, they may prove therapeutically useful as universal B-cell suppressants.
由小鼠mb-1和B29基因编码的两个共价连接的跨膜分子，已被确定为B细胞上表达的抗体受体单位的组成成分。我们制备了针对小鼠B29产物假定的人类等效物上一个暴露的细胞外表位的单克隆抗体。这些抗体CB3-1和CB3-2被用于证明该分子的细胞质表达在人类前B细胞（末端脱氧核苷酸转移酶阳性、μ链阴性）中开始，而表面表达则与所有同种型的表面免疫球蛋白表达严格一致。对人类免疫球蛋白相关分子的免疫化学分析显示，其分子异质性比小鼠类似物更为明显。免疫球蛋白相关分子的这种分子异质性随分化阶段以及B系细胞表达的免疫球蛋白同种型而变化。我们的数据支持这样一种假说，即表面免疫球蛋白相关分子的生化异质性可能导致不同成熟阶段B细胞上抗原受体交联的生物学效应存在差异。由于CB3抗体能够下调所有B细胞上的抗原受体，它们可能被证明作为通用的B细胞抑制剂具有治疗用途。
