Increased development of T-bet+CD11c+ B cells predisposes to lupus in females : Analysis in BXD2 mouse and genetic crosses
Published by Elsevier Inc.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 257(2023) vom: 19. Dez., Seite 109842 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2023
|
| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural B cell(2) Genetic variants(4) Type I interferon(5) autoantibodies(6) lupus(1) sex(3) Autoantibodies |
| Zusammenfassung: | Published by Elsevier Inc. 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/6J) x BXD2. Sex was the key factor leading to increased total IgG, IgG2b, and autoantibodies. The percentage of T-bet+CD11c+ IgD+ activated naive B cells (aNAV) was higher in females and was associated with increased T-bet+CD11c+ IgD- age-related B cells, Fas+GL7+ germinal center B cells, Cxcr5-Icos+ peripheral T-helper cells, and Cxcr5+Icos+ 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 |
|---|---|
| Beschreibung: | Date Completed 21.12.2023 Date Revised 20.10.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2023.109842 |