Paulie S, Rosén A, Ehlin-Henriksson B, Braesch-Andersen S, Jakobson E, Koho H, Perlmann P
Department of Immunology, University of Stockholm, Sweden.
J Immunol. 1989 Jan 15;142(2):590-5.
The human B lymphocyte and carcinoma-associated Ag, CDw40, (p50, Bp50) is a receptor candidate for normal growth regulation. Interaction of mAb with this pan-B Ag, together with preactivating agents such as 12-O-tetradecanoylphorbol-13-acetate or anti-mu, deliver strong growth-promoting signals to the cells. We here demonstrate that signaling through this Ag is dependent on its aggregation on the cell surface. Thus, monovalent antibody fragments were relatively inefficient in this respect but effectively blocked stimulation by intact antibody. By using affinity purified CDw40 protein we have also demonstrated that it is antigenically distinct from other B cell-associated Ag, including the six differentiation clusters CD19 to CD24. The mAb S2C6 and G28.5, prepared by immunizing mice with human bladder carcinoma cells or tonsillar B-cells, respectively, were the only antibodies giving detectable binding. Either of these antibodies could also completely block the binding of the other, suggesting an identity or structural proximity of the epitopes recognized. The CDw40 Ag was shown to be a phosphoprotein lacking intrinsic protein kinase activity. The results provide further evidence for CDw40 being an important B cell growth factor receptor which may also have growth regulatory functions in the development of certain human carcinomas.
人类B淋巴细胞及癌相关抗原CDw40（p50，Bp50）是正常生长调节的候选受体。单克隆抗体与这种全B抗原相互作用，再加上如十四酰佛波醇乙酯或抗μ等预激活剂，可向细胞传递强烈的促生长信号。我们在此证明，通过该抗原的信号传导依赖于其在细胞表面的聚集。因此，单价抗体片段在这方面相对低效，但能有效阻断完整抗体的刺激。通过使用亲和纯化的CDw40蛋白，我们还证明它在抗原性上与其他B细胞相关抗原不同，包括六个分化簇CD19至CD24。分别用人膀胱癌细胞或扁桃体B细胞免疫小鼠制备的单克隆抗体S2C6和G28.5是唯一能产生可检测结合的抗体。这两种抗体中的任何一种也能完全阻断另一种抗体的结合，表明所识别的表位相同或结构相近。CDw40抗原被证明是一种缺乏内在蛋白激酶活性的磷蛋白。这些结果为CDw40作为一种重要的B细胞生长因子受体提供了进一步的证据，它可能在某些人类癌症的发展中也具有生长调节功能。
