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.
Original language | English (US) |
---|---|
Article number | 701066 |
Pages (from-to) | 701066 |
Number of pages | 14 |
Journal | Frontiers in immunology |
Volume | 12 |
DOIs | |
State | Published - Jul 16 2021 |
Keywords
- autoantibody
- autophagy
- autoreactive memory B cells
- glomerulonephritis
- lupus
- memory B cells
- pristane induced lupus
- systemic autoimmunity
- Memory B Cells/immunology
- Autophagy/immunology
- Autoantigens/immunology
- Autoantibodies/immunology
- Terpenes/toxicity
- Mice, Inbred MRL lpr
- Animals
- Autoimmunity/immunology
- Mice
- Lupus Erythematosus, Systemic/chemically induced
- Disease Models, Animal
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology