Björck P, Axelsson B, Paulie S
Department of Immunology, Stockholm University, Sweden.
Scand J Immunol. 1991 Feb;33(2):211-8. doi: 10.1111/j.1365-3083.1991.tb03751.x.
CD40 and CD43 are two cell-surface glycoproteins that appear to be functionally involved in the growth stimulation of human B cells. Whereas CD40 is structurally similar to the NGF receptor and is present on all resting B cells, CD43 displays no homology to other known proteins and is expressed only on a subpopulation of these cells. To further understand the extra- and intracellular signals regulating these molecules and in which stage of activation they may play a role, we used various activation strategies and studied their expression on tonsillar B cells. As expected, activation of protein kinase C by TPA increased both CD40 and CD43. In contrast, a rise in intracellular Ca2+, e.g. by ionomycin, did not influence the expression of these antigens. However, in the presence of TPA, ionomycin further up-regulated CD43 but not CD40. Anti-IgM behaved similarly to ionomycin suggesting that the effect of this reagent was due primarily to its ability to increase intracellular Ca2+. Of three interleukins (IL-2, IL-4 and IL-6) only IL-4 had a significant effect when used alone in that it up-regulated CD40 but not CD43. However, in the presence of anti-IgM, both IL-2 and IL-4 synergistically up-regulated the two antigens. Complementation of antigen receptor stimulation with TPA or IL-4 increased CD40 during the first 24 h, whereas up-regulation of CD43 did not occur until 24 to 48 h after stimulation. With regard both to up-regulation in response to different stimuli and to kinetics, CD40 expression paralleled that of the early activation antigen CD23, whereas CD43 was induced in parallel with the transferrin receptor (CD71). Taken together, our results suggests that the expression of CD40 and CD43 is regulated by different intracellular signals and that CD40 may be important during early activation, whereas CD43 may have its major function during later stages of B-cell differentiation. These assumptions are in line with the observations that CD40 antibodies can directly activate resting B cells and that CD43 are retained on plasma cells.
CD40和CD43是两种细胞表面糖蛋白，似乎在人B细胞的生长刺激中发挥功能作用。虽然CD40在结构上与神经生长因子（NGF）受体相似，且存在于所有静息B细胞上，但CD43与其他已知蛋白无同源性，仅在这些细胞的一个亚群上表达。为了进一步了解调节这些分子的细胞外和细胞内信号以及它们可能在激活的哪个阶段发挥作用，我们采用了各种激活策略，并研究了它们在扁桃体B细胞上的表达。正如预期的那样，佛波酯（TPA）激活蛋白激酶C会增加CD40和CD43的表达。相反，细胞内Ca2+升高，如通过离子霉素处理，并不影响这些抗原的表达。然而，在存在TPA的情况下，离子霉素进一步上调了CD43，但没有上调CD40。抗IgM的作用与离子霉素相似，表明该试剂的作用主要是由于其增加细胞内Ca2+的能力。在三种白细胞介素（IL-2、IL-4和IL-6）中，只有IL-4单独使用时有显著作用，它上调了CD40但没有上调CD43。然而，在存在抗IgM的情况下，IL-2和IL-4协同上调了这两种抗原。用TPA或IL-4补充抗原受体刺激在最初24小时内增加了CD40的表达，而CD43的上调直到刺激后24至48小时才出现。关于对不同刺激的上调反应和动力学，CD40的表达与早期激活抗原CD23的表达平行，而CD43的诱导与转铁蛋白受体（CD71）平行。综上所述，我们的结果表明，CD40和CD43的表达受不同的细胞内信号调节，并且CD40在早期激活过程中可能很重要，而CD43可能在B细胞分化的后期阶段发挥主要功能。这些假设与以下观察结果一致：CD40抗体可直接激活静息B细胞，且CD43保留在浆细胞上。
