biostudies-literatureRicker EPeter Jay Sharp FoundationMarina Kellen French and the Anna-Maria and Stephen Kellen FoundationRheumatology Research FoundationU.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin DiseasesBarbara Volcker Center Giammaria Giuliani and the Ambrose Monell FoundationLupus Research AllianceNCI NIH HHSNIAMS NIH HHSNIH HHS4813https://www.ebi.ac.uk/biostudies/studies/S-EPMC8355159biostudies-literatureUnknown12(1)Differences in immune responses to viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) can show sexual dimorphism. Age-associated B cells (ABC) are a population of CD11c⁺T-bet⁺ B cells critical for antiviral responses and autoimmune disorders. Absence of DEF6 and SWAP-70, two homologous guanine exchange factors, in double-knock-out (DKO) mice leads to a lupus-like syndrome in females marked by accumulation of ABCs. Here we demonstrate that DKO ABCs show sex-specific differences in cell number, upregulation of an ISG signature, and further differentiation. DKO ABCs undergo oligoclonal expansion and differentiate into both CD11c⁺ and CD11c^- effector B cell populations with pathogenic and pro-inflammatory function as demonstraNature communicationsAltered function and differentiation of age-associated B cells contribute to the female bias in lupus mice.PMC8355159P30 CA016520AR064883T32 AR071302R01 AR064883AR070146R01 AR070146S10 OD019986Ricker EGupta SJenkins DRivera-Correa JPannellini TManni MSculco PKFlores-Castro DJessberger RMeng WRosenfeld AMPrak ETLPernis ABChinenov YBachu MfalseAltered function and differentiation of age-associated B cells contribute to the female bias in lupus mice.Differences in immune responses to viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) can show sexual dimorphism. Age-associated B cells (ABC) are a population of CD11c⁺T-bet⁺ B cells critical for antiviral responses and autoimmune disorders. Absence of DEF6 and SWAP-70, two homologous guanine exchange factors, in double-knock-out (DKO) mice leads to a lupus-like syndrome in females marked by accumulation of ABCs. Here we demonstrate that DKO ABCs show sex-specific differences in cell number, upregulation of an ISG signature, and further differentiation. DKO ABCs undergo oligoclonal expansion and differentiate into both CD11c⁺ and CD11c^- effector B cell populations with pathogenic and pro-inflammatory function as demonstra2021-01-01T00:00:00Z2021 Aug2026-05-08T13:48:16.644Z2025-05-18T11:57:36.744ZS-EPMC83551593437666410.1038/s41467-021-25102-8