Upregulated Fcrl5 Disrupts B Cell Anergy and Causes Autoimmune Disease

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Oct 16

PMID 37841260

Authors

Chisato Ono

Shinya Tanaka

Keiko Myouzen

Takeshi Iwasaki

Mahoko Ueda

Yoshinao Oda

Kazuhiko Yamamoto

Yuta Kochi

Yoshihiro Baba

Affiliations

Soon will be listed here.

Abstract

B cell anergy plays a critical role in maintaining self-tolerance by inhibiting autoreactive B cell activation to prevent autoimmune diseases. Here, we demonstrated that Fc receptor-like 5 (Fcrl5) upregulation contributes to autoimmune disease pathogenesis by disrupting B cell anergy. Fcrl5-a gene whose homologs are associated with human autoimmune diseases-is highly expressed in age/autoimmunity-associated B cells (ABCs), an autoreactive B cell subset. By generating B cell-specific Fcrl5 transgenic mice, we demonstrated that Fcrl5 overexpression in B cells caused systemic autoimmunity with age. Additionally, Fcrl5 upregulation in B cells exacerbated the systemic lupus erythematosus-like disease model. Furthermore, an increase in Fcrl5 expression broke B cell anergy and facilitated toll-like receptor signaling. Thus, Fcrl5 is a potential regulator of B cell-mediated autoimmunity by regulating B cell anergy. This study provides important insights into the role of Fcrl5 in breaking B cell anergy and its effect on the pathogenesis of autoimmune diseases.

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