Faculty, Staff and Student Publications
Language
English
Publication Date
8-7-2023
Journal
Journal of Experimental Medicine
DOI
10.1084/jem.20221483
PMID
37097293
PMCID
PMC10130905
PubMedCentral® Posted Date
4-25-2023
Abstract
The formation of germinal centers (GCs) is crucial for humoral immunity and vaccine efficacy. Constant stimulation through microbiota drives the formation of constitutive GCs in Peyer's patches (PPs), which generate B cells that produce antibodies against gut antigens derived from commensal bacteria and infectious pathogens. However, the molecular mechanism that regulates this persistent process is poorly understood. We report that Ewing Sarcoma Breakpoint Region 1 (EWSR1) is a brake to constitutive GC generation and immunoglobulin G (IgG) production in PPs, vaccination-induced GC formation, and IgG responses. Mechanistically, EWSR1 suppresses Bcl6 upregulation after antigen encounter, thereby negatively regulating induced GC B cell generation and IgG production. We further showed that tumor necrosis factor receptor-associated factor (TRAF) 3 serves as a negative regulator of EWSR1. These results established that the TRAF3-EWSR1 signaling axis acts as a checkpoint for Bcl6 expression and GC responses, indicating that this axis is a therapeutic target to tune GC responses and humoral immunity in infectious diseases.
Keywords
Antigens, B-Lymphocytes, Germinal Center, Immunoglobulin G, Peyer's Patches, TNF Receptor-Associated Factor 3, Humans, RNA-Binding Protein EWS
Published Open-Access
yes
Recommended Citation
Li, Yanchuan; Zhu, Lele; Ko, Chun-Jung; et al., "TRAF3-EWSR1 Signaling Axis Acts as a Checkpoint on Germinal Center Responses" (2023). Faculty, Staff and Student Publications. 6618.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6618
Graphical Abstract
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons
Comments
This article has been corrected. See J Exp Med. 2023 Jul 18;220(8):e2022148307122023c.