| Title: |
Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice |
| Authors: |
Ricker, Edd; Manni, Michela; Flores-Castro, Danny; Jenkins, Daniel; Gupta, Sanjay; Rivera-Correa, Juan; Meng, Wenzhao; Rosenfeld, Aaron M.; Pannellini, Tania; Bachu, Mahesh; Chinenov, Yurii; Sculco, Peter K.; Jessberger, Rolf; Prak, Eline T. Luning; Pernis, Alessandra B. |
| Contributors: |
Barbara Volcker Center Giammaria Giuliani and the Ambrose Monell Foundation; Marina Kellen French and the Anna-Maria and Stephen Kellen Foundation; U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases; Rheumatology Research Foundation; Lupus Research Alliance; Peter Jay Sharp Foundation |
| Source: |
Nature Communications ; volume 12, issue 1 ; ISSN 2041-1723 |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2021 |
| Description: |
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 demonstrated by BCR sequencing and fate-mapping experiments. Tlr7 duplication in DKO males overrides the sex-bias and further augments the dissemination and pathogenicity of ABCs, resulting in severe pulmonary inflammation and early mortality. Thus, sexual dimorphism shapes the expansion, function and differentiation of ABCs that accompanies TLR7-driven immunopathogenesis. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41467-021-25102-8 |
| Availability: |
https://doi.org/10.1038/s41467-021-25102-8; https://www.nature.com/articles/s41467-021-25102-8.pdf; https://www.nature.com/articles/s41467-021-25102-8 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.5717BF21 |
| Database: |
BASE |