Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice

Edd Ricker, Michela Manni, Danny Flores-Castro, Daniel Jenkins, Sanjay Gupta, Juan Rivera-Correa, Wenzhao Meng, Aaron M. Rosenfeld, Tania Pannellini, Mahesh Bachu, Yurii Chinenov, Peter K. Sculco, Rolf Jessberger, Eline T. Luning Prak and Alessandra B. Pernis ()
Additional contact information
Edd Ricker: Hospital for Special Surgery
Michela Manni: Hospital for Special Surgery
Danny Flores-Castro: Hospital for Special Surgery
Daniel Jenkins: Hospital for Special Surgery
Sanjay Gupta: Hospital for Special Surgery
Juan Rivera-Correa: Hospital for Special Surgery
Wenzhao Meng: Perelman School of Medicine
Aaron M. Rosenfeld: Perelman School of Medicine
Tania Pannellini: Hospital for Special Surgery
Mahesh Bachu: Hospital for Special Surgery
Yurii Chinenov: Hospital for Special Surgery
Peter K. Sculco: Hospital for Special Surgery
Rolf Jessberger: Technische Universitat
Eline T. Luning Prak: Perelman School of Medicine
Alessandra B. Pernis: Hospital for Special Surgery

Nature Communications, 2021, vol. 12, issue 1, 1-21

Abstract: Abstract 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25102-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25102-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25102-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().