Defective IgG Class Switching in the Spleen of TRAF5-Deficient Mice Reveals a Role for TRAF5 in CD40-Mediated B Cell Responses During Obesity-Associated Inflammation.

Tumor necrosis factor receptor-associated factors (TRAFs) are a family of adaptor proteins that transmit signals from immunoregulatory receptors-such as TNF receptors, Toll-like receptors, and interleukin receptors-to coordinate immune and inflammatory responses. Among them, TRAF5 is highly expressed in lymphocytes and implicated in obesity-associated inflammation, but its role in secondary lymphoid organs during chronic low-grade inflammation remains unclear. We examined splenic B and T cell phenotypes in wild-type (WT) and Traf5-deficient (KO) mice fed a high-fat diet (HFD). Although lymphocyte composition was broadly comparable, KO mice showed reduced spontaneous immunoglobulin G2c (IgG2c) production ex vivo-about 1.5-fold lower than WT. Notably, despite elevated TNF-α and CD40 ligand (CD40L) expression in HFD-fed KO splenocytes, IgG2c production remained diminished-about 1.9-fold lower than WT-upon soluble CD40L stimulation, indicating impaired CD40-mediated class-switch recombination (CSR). Consistently, B cells from KO mice on a normal diet exhibited reduced activation-induced cytidine deaminase (AID) expression-about 4.4-fold lower than WT-after CD40L stimulation, and decreased IgG2c secretion-about 6.6-fold lower-upon CD40L and IFN-γ co-stimulation in vitro. Collectively, these findings suggest that TRAF5 is involved in CD40-dependent CSR in B cells under inflammatory conditions and may contribute to sustaining adaptive immune responses during obesity-associated chronic inflammation.