| First Author | Woolaver RA | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 11 | Pages | 3421-3430 |
| PubMed ID | 30341187 | Mgi Jnum | J:266996 |
| Mgi Id | MGI:6257927 | Doi | 10.4049/jimmunol.1800337 |
| Citation | Woolaver RA, et al. (2018) TRAF2 Deficiency in B Cells Impairs CD40-Induced Isotype Switching That Can Be Rescued by Restoring NF-kappaB1 Activation. J Immunol 201(11):3421-3430 |
| abstractText | Effective humoral immunity requires class switch recombination (CSR) catalyzed by activation-induced cytidine deaminase (AID). In response to T cell-dependent (TD) Ags, CSR can be induced by CD40 signaling in B cells. TNFR-associated factors 2 and 3 (TRAF2/TRAF3) function as adaptors of the CD40 signaling pathway. B cell-intrinsic TRAF2 or TRAF3 (B-TRAF2 or B-TRAF3) knockout mice were previously reported to have indistinguishable phenotypes in gene expression, B cell survival and development, and enlarged peripheral lymphoid organs. However, it remains unknown whether deficiency of B-TRAF2 or B-TRAF3 differentially affects TD humoral immune responses and CD40-induced CSR. In this article, we show that B-TRAF2 is essential for optimal isotype switching induced by in vivo TD Ag immunization or by engaging CD40 in vitro. Our data clarify the controversial role of B-TRAF3 and confirm its dispensability in CD40-induced CSR. Mechanistically, CD40-induced AID expression was markedly impaired by B-TRAF2, but not B-TRAF3, deficiency. Moreover, B-TRAF2 deficiency causes defective activation of the NF-kappaB1 complex in a CD40-autonomous manner, and restoring CD40-induced NF-kappaB1 activation in TRAF2-deficient B cells rescues AID expression and CSR. We conclude that TRAF2 is essential but TRAF3 is dispensable for TD humoral immunity and CD40-induced CSR. Our studies provide significant biological bases for optimizing treatment of B cell-associated immune disorders by targeting CD40 signaling. |
