Journal
JOURNAL OF IMMUNOLOGY
Volume 199, Issue 8, Pages 2618-2623Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1700888
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Funding
- National Institutes of Health (NIH) [R01-AI-071110]
- Veterans Administration Merit Review Grant [1I01BX000600]
- NIH [R01-AI-083705, P30-AR-048311, P30-AI-027767]
- NIH Immunology T32 Training Grant [2T32AI007051-39]
- Lupus Foundation of America Finzi Summer Fellowship
- Lupus Research Institute Novel Research Award
- Tier 1 Canada Research Chair grant
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The transitional stage of B cell development is a formative stage in the spleen where autoreactive specificities are censored as B cells gain immune competence, but the intrinsic and extrinsic factors regulating survival of transitional stage 1 (T1) B cells are unknown. We report that B cell expression of IFN-beta is required for optimal survival and TLR7 responses of transitional B cells in the spleen and was overexpressed in T1 B cells from BXD2 lupus-prone mice. Single-cell gene expression analysis of B6 Ifnb(+/+) versus B6 Ifnb(-/-) T1 B cells revealed heterogeneous expression of Ifnb in wild-type B cells and distinct gene expression patterns associated with endogenous IFN-beta. Single-cell analysis of BXD2 T1 B cells revealed that Ifnb is expressed in early T1 B cell development with subsequent upregulation of Tlr7 and Ifna1. Together, these data suggest that T1 B cell expression of IFN-beta plays a key role in regulating responsiveness to external factors.
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