Lupus-associated innate receptors drive extrafollicular evolution of autoreactive B cells.

ABSTRACT: In systemic lupus erythematosus, recent findings highlight the extrafollicular (EF) pathway as prominent origin of autoantibody-secreting cells (ASCs). CD21^loCD11c⁺ B cells, associated with aging, infection, and autoimmunity, are contributors to autoreactive EF ASCs but have an obscure developmental trajectory. To study EF kinetics of autoreactive B cell in tissue, we adoptively transferred WT and gene knockout B cell populations into the 564Igi mice - an autoreactive host enriched with autoantigens and T cell help. Time-stamped analyses revealed TLR7 dependence in early escape of peripheral B cell tolerance and establishment of a pre-ASC division program. We propose CD21^lo cells as precursors to EF ASCs due to their elevated TLR7 sensitivity and proliferat

SUBMITTER: Zhu DY 

PROVIDER: S-EPMC10802414 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature