Cutting Edge: Endogenous IFN-β Regulates Survival and Development of Transitional B Cells

J Immunol. 2017 Oct 15;199(8):2618-2623. doi: 10.4049/jimmunol.1700888. Epub 2017 Sep 13.

Abstract

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-β 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-β. 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-β plays a key role in regulating responsiveness to external factors.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Survival
  • Disease Susceptibility
  • Interferon beta-1a / genetics
  • Interferon beta-1a / metabolism
  • Interferon-alpha
  • Interferon-beta / metabolism*
  • Lupus Nephritis / immunology*
  • Lymphocyte Activation
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred Strains
  • Precursor Cells, B-Lymphoid / immunology*
  • Single-Cell Analysis
  • Spleen / immunology*
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / metabolism

Substances

  • Ifna1 protein, mouse
  • Interferon-alpha
  • Membrane Glycoproteins
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Interferon-beta
  • Interferon beta-1a