TRAF3-EWSR1 Signaling Axis Acts As a Checkpoint on Germinal Center Responses

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2023 Apr 25

PMID 37097293

Authors

Yanchuan Li

Lele Zhu

Chun-Jung Ko

Jin-Young Yang

Hongjiao Wang

Ganiraju Manyam

Jing Wang

Xuhong Cheng

Shuli Zhao

Zuliang Jie

Affiliations

Soon will be listed here.

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.

Citing Articles

PGRN Inhibits Early B-cell Activation and IgE Production Through the IFITM3-STAT1 Signaling Pathway in Asthma.

Zhang P, Ruan C, Yang G, Guan Y, Zhu Y, Li Q Adv Sci (Weinh). 2024; 11(45):e2403939.

PMID: 39412083 PMC: 11615816. DOI: 10.1002/advs.202403939.

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