Hostager B S, Bishop G A
Department of Microbiology, University of Iowa, VA Medical Center, Iowa City 52242, USA.
J Immunol. 1999 Jun 1;162(11):6307-11.
In B lymphocytes, CD40 signals contribute to the activation of Ab secretion, isotype switching, T cell costimulation, and immunological memory. TRAF proteins appear to be important components of the CD40 signal transduction complex, but their roles in the activation of B cell effector functions are poorly understood. We examined the contributions of TNF receptor-associated factor 2 (TRAF2) and TRAF3 to CD40-activated differentiation in mouse B cells transfected with inducible TRAF and dominant-negative TRAF cDNAs. We find that binding of TRAF2 and TRAF3 to CD40 is not required for the induction of Ab secretion, but that both TRAF molecules can regulate the activation process. We demonstrate a negative regulatory role for TRAF3 and that this activity is dependent on the availability of an intact TRAF3-binding site in the cytoplasmic domain of CD40. In contrast, TRAF2 appears to play a positive role in B cell differentiation, and this activity is apparent even when its binding site on CD40 is disrupted.
在B淋巴细胞中，CD40信号有助于抗体分泌的激活、同种型转换、T细胞共刺激和免疫记忆。肿瘤坏死因子受体相关因子（TRAF）蛋白似乎是CD40信号转导复合物的重要组成部分，但它们在B细胞效应功能激活中的作用尚不清楚。我们用可诱导的TRAF和显性负性TRAF cDNA转染小鼠B细胞，研究了肿瘤坏死因子受体相关因子2（TRAF2）和TRAF3对CD40激活的分化的作用。我们发现，诱导抗体分泌并不需要TRAF2和TRAF3与CD40结合，但这两种TRAF分子都可以调节激活过程。我们证明了TRAF3的负调节作用，并且这种活性依赖于CD40胞质结构域中完整TRAF3结合位点的可用性。相反，TRAF2似乎在B细胞分化中起积极作用，即使其在CD40上的结合位点被破坏，这种活性也很明显。
