Journal Article

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

Iwata, Chieri, So, Takanori, Wada, Tsutomu, Sato, Ayaka, Hikosaka-Kuniishi, Mari, Morita, Masashi, Ozawa, Yusuke, Wakaizumi, Tomomi, Sasaoka, Toshiyasu

2025

Overview

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.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Animals / Antibodies / Atherosclerosis / Autoimmune diseases / B cells / B-Lymphocytes - immunology / B-Lymphocytes - metabolism / Body fat / Cardiovascular disease / CD40 Antigens - immunology / CD40 Antigens - metabolism / Cytokines / Diet, High-Fat - adverse effects / Fatty acids / Fatty liver / Gastrointestinal surgery / Homeostasis / Hypertension / Immune response / Immunity (Disease) / Immunoglobulin Class Switching / Immunoglobulin G / Immunoglobulin G - genetics / Immunoglobulin G - immunology / Immunoglobulins / Inflammation / Inflammation - etiology / Inflammation - genetics / Inflammation - immunology / Inflammation - metabolism / Insulin resistance / Interleukins / Lipids / Liver diseases / Lymphocytes / Male / Metabolism / Mice / Mice, Inbred C57BL / Mice, Knockout / Obesity / Obesity - complications / Obesity - genetics / Obesity - immunology / Obesity - metabolism / Spleen / Spleen - immunology / Spleen - metabolism / T cells / TNF Receptor-Associated Factor 5 - deficiency / TNF Receptor-Associated Factor 5 - genetics / TNF Receptor-Associated Factor 5 - metabolism / Tumor necrosis factor / Tumor necrosis factor-TNF