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Peer-reviewedCC BY-NC-NDCell Reports

Female mice with a Xist deletion in B cells can develop lupus-associated phenotypes

  • Claudia D. Lovell1
  • Nikhil Jiwrajka2
  • Natalie E. Toothacre1
  • Hayley K. Amerman3
  • Michael P. Cancro4
  • Montserrat C. Anguera5
5 affiliations
  1. 1Department of Biomedical Science, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  2. 2Department of Biomedical Science, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Rheumatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  3. 3Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  4. 4Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  5. 5Department of Biomedical Science, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected]
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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease preferentially observed in women. X-linked gene expression in XX females is equalized with that in XY males by X chromosome inactivation (XCI). However, B cells from female patients with SLE and mouse models of SLE exhibit aberrant X-linked gene expression and mislocalization of Xist RNA, a critical regulator of XCI, suggesting that impaired XCI may contribute to the disease. Here, some female mice harboring a B cell-specific Xist deletion ("Xist cKO") spontaneously developed SLE phenotypes, including expanded activated B cell subsets, disease-specific autoantibodies, and glomerulonephritis. Pristane treatment of Xist cKO mice led to an increased expansion of activated B cell subsets, resulting in higher anti-dsDNA autoantibody production. Activated B cells from Xist cKO mice with SLE phenotypes had an increased expression of X-linked and autosomal genes, depletion of X-linked H3K27me3, and were more responsive to stimulation. This work suggests that impaired XCI maintenance in B cells directly contributes to SLE-associated phenotypes in a female-biased manner.

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Cite

BibTeXRIS
BibTeX
@article{lovell2026female,
  title = {{Female mice with a Xist deletion in B cells can develop lupus-associated phenotypes}},
  author = {Claudia D. Lovell and Nikhil Jiwrajka and Natalie E. Toothacre and Hayley K. Amerman and Michael P. Cancro and Montserrat C. Anguera},
  journal = {Cell Reports},
  year = {2026},
  month = jun,
  doi = {10.1016/j.celrep.2026.117517},
  url = {https://doi.org/10.1016/j.celrep.2026.117517},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Female mice with a Xist deletion in B cells can develop lupus-associated phenotypes
AU  - Claudia D. Lovell
AU  - Nikhil Jiwrajka
AU  - Natalie E. Toothacre
AU  - Hayley K. Amerman
AU  - Michael P. Cancro
AU  - Montserrat C. Anguera
PY  - 2026
DA  - 2026/06/01
JO  - Cell Reports
DO  - 10.1016/j.celrep.2026.117517
UR  - https://doi.org/10.1016/j.celrep.2026.117517
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease preferentially observed in women. X-linked gene expression in XX females is equalized with that in XY males by X chromosome inactivation (XCI). However, B cells from female patients with SLE and mouse models of SLE exhibit aberrant X-linked gene expression and mislocalization of Xist RNA, a critical regulator of XCI, suggesting that impaired XCI may contribute to the disease. Here, some female mice harboring a B cell-specific Xist deletion ("Xist cKO") spontaneously developed SLE phenotypes, including expanded activated B cell subsets, disease-specific autoantibodies, and glomerulonephritis. Pristane treatment of Xist cKO mice led to an increased expansion of activated B cell subsets, resulting in higher anti-dsDNA autoantibody production. Activated B cells from Xist cKO mice with SLE phenotypes had an increased expression of X-linked and autosomal genes, depletion of X-linked H3K27me3, and were more responsive to stimulation. This work suggests that impaired XCI maintenance in B cells directly contributes to SLE-associated phenotypes in a female-biased manner.
SN  - 2211-1247
SN  - 2639-1856
ER  -