Lunatic, manic, and radical fringe each promote T and B cell development

Yinghui Song, Kumar Vivek, Hua Xing Wei, Ju Qiu, Pamela Stanley

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Lunatic, Manic, and Radical Fringe (LFNG, MFNG, and RFNG) are N-acetylglucosaminyltransferases that modify Notch receptors and regulate Notch signaling. Loss of LFNG affects thymic T cell development, and LFNG and MFNG are required for marginal zone (MZ) B cell development. However, roles for MFNG and RFNG in T cell development, RFNG in B cell development, or Fringes in T and B cell activation are not identified. In this study, we show that Lfng/Mfng/Rfng triple knockout (Fng tKO) mice exhibited reduced binding of DLL4 Notch ligand to CD4/CD8 double-negative (DN) T cell progenitors, and reduced expression of NOTCH1 targets Deltex1 and CD25. Fng tKO mice had reduced frequencies of DN1/cKit+ and DN2 T cell progenitors and CD4+CD8+ double-positive (DP) T cell precursors, but increased frequencies of CD4+ and CD8+ single-positive T cells in the thymus. In spleen, Fng tKO mice had reduced frequencies of CD4+, CD8+, central memory T cells and MZ B cells, and an increased frequency of effector memory T cells, neutrophils, follicular, and MZ P B cells. The Fng tKO phenotype was cell-autonomous and largely rescued in mice expressing one allele of a single Fng gene. Stimulation of Fng tKO splenocytes with anti-CD3/CD28 beads or LPS gave reduced proliferation compared with controls, and the generation of activated T cells by Concanavalin A or L-PHA was also reduced in Fng tKO mice. Therefore, each Fringe contributes to Tand B cell development, and Fringe is required for optimal in vitro stimulation of T and B cells.

Original languageEnglish (US)
Pages (from-to)232-243
Number of pages12
JournalJournal of Immunology
Volume196
Issue number1
DOIs
StatePublished - Jan 1 2016

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B-Lymphocytes
T-Lymphocytes
N-Acetylglucosaminyltransferases
Notch Receptors
T-Lymphoid Precursor Cells
Concanavalin A
Thymus Gland
Neutrophils
Spleen
Alleles
Ligands
Phenotype
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Lunatic, manic, and radical fringe each promote T and B cell development. / Song, Yinghui; Vivek, Kumar; Wei, Hua Xing; Qiu, Ju; Stanley, Pamela.

In: Journal of Immunology, Vol. 196, No. 1, 01.01.2016, p. 232-243.

Research output: Contribution to journalArticle

Song, Yinghui ; Vivek, Kumar ; Wei, Hua Xing ; Qiu, Ju ; Stanley, Pamela. / Lunatic, manic, and radical fringe each promote T and B cell development. In: Journal of Immunology. 2016 ; Vol. 196, No. 1. pp. 232-243.
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