Barrett T B, Shu G L, Draves K E, Pezzutto A, Clark E A
Department of Microbiology, University of Washington, Seattle 98195.
Eur J Immunol. 1990 May;20(5):1053-9. doi: 10.1002/eji.1830200516.
To understand further the roles that negative regulatory signals may play in B cell immune responses, we compared three inhibitors of B cell proliferation: cross-linking CD19 with monoclonal antibody (mAb), signaling through Fc receptors by intact anti-mu mAb, and transforming growth factor-beta (TGF-beta). Each agent was tested for its ability to block proliferation and specific activation events induced in human tonsilar B cells activated by either cross-linking surface immunoglobulin, signaling through CD20, or direct activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate. We found that each inhibitor was functionally distinct. Both anti-CD19 mAb and anti-mu mAb inhibited anti-immunoglobulin activated cells and anti-CD20-activated cells, but neither inhibited cells activated by phorbol 12-myristate 13-acetate. TGF-beta, on the other hand, inhibited equally profoundly cells activated by each of the three regimens. These results suggest that TGF-beta blocks B cell activation at a step following the activation of PKC, whereas both signaling through CD19 and Fc receptor block early steps in the PKC activation pathway. Signaling through anti-CD19 mAb was unique in that proliferation of anti-immunoglobulin-activated cells was reduced on day 3 and then augmented subsequently. With all other inhibitory combinations the block was permanent. We conclude that each of these three inhibitors has unique important functions and therefore suggest that the effectiveness of negative signaling in B cell immune regulation will depend on the combinations of specific inhibitors modulating a specific activation program.
为了进一步了解负调控信号在B细胞免疫反应中可能发挥的作用，我们比较了三种B细胞增殖抑制剂：用单克隆抗体（mAb）交联CD19、完整的抗μ mAb通过Fc受体发出信号以及转化生长因子-β（TGF-β）。测试了每种试剂阻断人扁桃体B细胞增殖和特异性激活事件的能力，这些B细胞通过交联表面免疫球蛋白、通过CD20发出信号或用佛波醇12-肉豆蔻酸酯13-乙酸盐直接激活蛋白激酶C（PKC）而被激活。我们发现每种抑制剂在功能上都有所不同。抗CD19 mAb和抗μ mAb均抑制抗免疫球蛋白激活的细胞和抗CD20激活的细胞，但均不抑制由佛波醇12-肉豆蔻酸酯13-乙酸盐激活的细胞。另一方面，TGF-β同等程度地抑制了由这三种方案中的每一种激活的细胞。这些结果表明，TGF-β在PKC激活后的一个步骤阻断B细胞激活，而通过CD19和Fc受体发出的信号阻断PKC激活途径中的早期步骤。通过抗CD19 mAb发出的信号具有独特之处，即抗免疫球蛋白激活的细胞在第3天增殖减少，随后增加。对于所有其他抑制组合，阻断是永久性的。我们得出结论，这三种抑制剂中的每一种都具有独特的重要功能，因此表明B细胞免疫调节中负信号的有效性将取决于调节特定激活程序的特定抑制剂的组合。
