Dependence on Autophagy for Autoreactive Memory B Cells in the Development of Pristane-Induced Lupus.

Autor: Jang A; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States., Sharp R; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States., Wang JM; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States., Feng Y; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States., Wang J; Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston, TX, United States.; Department of Surgery, Weill Cornell Medical College, Cornell University, New York, NY, United States., Chen M; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2021 Jul 16; Vol. 12, pp. 701066. Date of Electronic Publication: 2021 Jul 16 (Print Publication: 2021).
DOI: 10.3389/fimmu.2021.701066
Abstrakt: The production of autoantibodies by autoreactive B cells plays a major role in the pathogenesis of lupus. Increases in memory B cells have been observed in human lupus patients and autoimmune lpr mice. Autophagy is required for the maintenance of memory B cells against viral infections; however, whether autophagy regulates the persistence of autoantigen-specific memory B cells and the development of lupus remains to be determined. Here we show that memory B cells specific for autoantigens can be detected in autoimmune lpr mice and a pristane-induced lupus mouse model. Interestingly, B cell-specific deletion of Atg7 led to significant loss of autoreactive memory B cells and reduced autoantibody production in pristane-treated mice. Autophagy deficiency also attenuated the development of autoimmune glomerulonephritis and pulmonary inflammation after pristane treatment. Adoptive transfer of wild type autoreactive memory B cells restored autoantibody production in Atg7-deficient recipients. These data suggest that autophagy is important for the persistence of autoreactive memory B cells in mediating autoantibody responses. Our results suggest that autophagy could be targeted to suppress autoreactive memory B cells and ameliorate humoral autoimmunity.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Jang, Sharp, Wang, Feng, Wang and Chen.)
Databáze: MEDLINE