Increased development of T-betCD11c B cells predisposes to lupus in females: Analysis in BXD2 mouse and genetic crosses.

Nov 20, 2023

Experts: Kathryn A Sullivan,Casey Chapman,Lu Lu,David Ashbrook,Yong Wang,Fatima K Alduraibi,Changming Lu,Chao-Wang Sun,Shanrun Liu,Robert W Williams,John D Mountz,Hui-Chen Hsu

Cardinal features of lupus include elevated B cell activation and autoantibody production with a female sex preponderance. We quantified interactions of sex and genetic variation on the development of autoimmune B-cell phenotypes and autoantibodies in the BXD2 murine model of lupus using a cohort of backcrossed progeny (BXD2 x C57BL/6 J) x BXD2. Sex was the key factor leading to increased total IgG, IgG2b, and autoantibodies. The percentage of T-betCD11c IgD activated naive B cells (aNAV) was higher in females and was associated with increased T-betCD11c IgD age-related B cells, FasGL7 germinal center B cells, Cxcr5Icos peripheral T-helper cells, and T-and Cxcr5Icos follicular T-helper cells. IFN-β was elevated in females. Variation in aNAV cells was mapped to Chr 7 in a locus that shows significant interactions between the female sex and heterozygous B/D variant. Our results suggest that activation of naive B cells forms the basis for the female-predominant development of autoantibodies in lupus-susceptible BXD2 mice.
Copyright © 2023. Published by Elsevier Inc.

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ABOUT THE EXPERTS

Kathryn A Sullivan,Casey Chapman,Lu Lu,David Ashbrook,Yong Wang,Fatima K Alduraibi,Changming Lu,Chao-Wang Sun,Shanrun Liu,Robert W Williams,John D Mountz,Hui-Chen Hsu

Kathryn A Sullivan

Department of Medicine, Division of Clinical Immunology and Rheumatology, the University of Alabama at Birmingham, Birmingham, AL, USA.

Casey Chapman

Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA.

Lu Lu

Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA.

David Ashbrook

Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA.

Yong Wang

Department of Medicine, Division of Clinical Immunology and Rheumatology, the University of Alabama at Birmingham, Birmingham, AL, USA.

Fatima K Alduraibi

Department of Medicine, Division of Clinical Immunology and Rheumatology, the University of Alabama at Birmingham, Birmingham, AL, USA.

Changming Lu

Department of Medicine, Division of Clinical Immunology and Rheumatology, the University of Alabama at Birmingham, Birmingham, AL, USA.

Chao-Wang Sun

Department of Medicine, Division of Clinical Immunology and Rheumatology, the University of Alabama at Birmingham, Birmingham, AL, USA.

Shanrun Liu

Department of Medicine, Division of Clinical Immunology and Rheumatology, the University of Alabama at Birmingham, Birmingham, AL, USA.

Robert W Williams

Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA.

John D Mountz

Department of Medicine, Division of Clinical Immunology and Rheumatology, the University of Alabama at Birmingham, Birmingham, AL, USA; Medicine Service, Birmingham Veterans Affairs Health Care System, Birmingham, AL, USA.

Hui-Chen Hsu

Department of Medicine, Division of Clinical Immunology and Rheumatology, the University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: hhsu@uabmc.edu.