Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease

Chisato Ono; Shinya Tanaka; Keiko Myouzen; Takeshi Iwasaki; Mahoko Ueda; Yoshinao Oda; Kazuhiko Yamamoto; Yuta Kochi; Yoshihiro Baba

doi:10.3389/fimmu.2023.1276014

Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease

Front Immunol. 2023 Sep 28:14:1276014. doi: 10.3389/fimmu.2023.1276014. eCollection 2023.

Authors

Chisato Ono¹, Shinya Tanaka¹, Keiko Myouzen², Takeshi Iwasaki³, Mahoko Ueda⁴, Yoshinao Oda³, Kazuhiko Yamamoto², Yuta Kochi⁴, Yoshihiro Baba¹

Affiliations

¹ Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
² Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
³ Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁴ Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

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.

Keywords: B cells; Fc receptor-like 5 (Fcrl5); age/autoimmunity-associated B cells; anergy; autoimmunity; immune tolerance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autoimmune Diseases*
Autoimmunity / genetics
B-Lymphocytes
Humans
Lupus Erythematosus, Systemic*
Mice
Mice, Transgenic
Receptors, Fc

Substances

Receptors, Fc
FcRH3 protein, mouse

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This work was partially supported by JSPS KAKENHI (JP18H02626, 19K22537, JP21H02753 to YB, JP22H03112, JP22K19547 to ST and 18790697 to YK), JSPS Fellows (JP21J20013 and JP22KJ2376 to CO), JST FOREST Program (JPMJFR210S to ST), Agency for Medical Research and Development (AMED) (JP19ek0410044 and JP19gm6110004 to YB), the Medical Research Center Initiative for High Depth Omics and RIIT (to YK and YB), Kato Memorial Bioscience Foundation, and The Naito Foundation (to YB).