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

Front Immunol. 2021 Jul 16:12:701066. doi: 10.3389/fimmu.2021.701066. eCollection 2021.

Abstract

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.

Keywords: autoantibody; autophagy; autoreactive memory B cells; glomerulonephritis; lupus; memory B cells; pristane induced lupus; systemic autoimmunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Autoimmunity / immunology*
  • Autophagy / immunology*
  • Disease Models, Animal
  • Lupus Erythematosus, Systemic / chemically induced
  • Lupus Erythematosus, Systemic / immunology*
  • Memory B Cells / immunology*
  • Mice
  • Mice, Inbred MRL lpr
  • Terpenes / toxicity

Substances

  • Autoantibodies
  • Autoantigens
  • Terpenes
  • pristane