Jabara Haifa, Laouini Dhafer, Tsitsikov Erdyni, Mizoguchi Emiko, Bhan Atul, Castigli Emanuela, Dedeoglu Fatma, Pivniouk Vadim, Brodeur Scott, Geha Raif
Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Immunity. 2002 Sep;17(3):265-76. doi: 10.1016/s1074-7613(02)00394-1.
To define the role of TRAF proteins in CD40-dependent isotype switching in B cells, we introduced wild-type (WT) and mutant CD40 transgenes that lacked the binding motifs for TRAF6 (CD40deltaTRAF6), TRAF2 and TRAF3 (CD40deltaTRAF2/3), or both (CD40deltaTRAFs) into B cells of CD40(-/-) mice. The in vivo isotype switch defect in CD40(-/-) mice was fully corrected by WT and CD40deltaTRAF6, partially by CD40deltaTRAF2/3, and not at all by CD40deltaTRAFs transgenes. CD40-mediated isotype switching, proliferation, and activation of p38, JNK, and NFkappaB in B cells were normal in WT and CD40deltaTRAF6 mice, severely impaired in CD40deltaTRAF2/3, and absent in CD40deltaTRAFs mice. These results suggest that binding to TRAF2 and/or TRAF3 but not TRAF6 is essential for CD40 isotype switching and activation in B cells.
为了确定TRAF蛋白在B细胞中CD40依赖性同种型转换中的作用，我们将缺乏TRAF6结合基序（CD40deltaTRAF6）、TRAF2和TRAF3结合基序（CD40deltaTRAF2/3）或两者结合基序（CD40deltaTRAFs）的野生型（WT）和突变型CD40转基因导入CD40(-/-)小鼠的B细胞中。WT和CD40deltaTRAF6可完全纠正CD40(-/-)小鼠的体内同种型转换缺陷，CD40deltaTRAF2/3可部分纠正，而CD40deltaTRAFs转基因则完全无法纠正。在WT和CD40deltaTRAF6小鼠中，B细胞中CD40介导的同种型转换、增殖以及p38、JNK和NFkappaB的激活均正常；在CD40deltaTRAF2/3小鼠中严重受损；在CD40deltaTRAFs小鼠中则不存在。这些结果表明，与TRAF2和/或TRAF3而非TRAF6结合对于B细胞中CD40同种型转换和激活至关重要。
