Cell extrinsic alterations in splenic b cell maturation in flt3-ligand knockout mice

Joseph J. Dolence, Kimberly A. Gwin, Mariya B. Shapiro, Fan Chi Hsu, Virginia M Shapiro, Kay L Medina

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

B lymphopoiesis in bone marrow (BM) is critical for maintaining a diverse peripheral B cell pool to fight infection and establish lifelong immunity. The generation of immature B cells is reduced in Flt3-ligand (FL-/-) mice leading to deficiencies in splenic B cells. Here, we sought to understand the cellular basis of the spleen B cell deficiency in FL-/-mice. Significant reductions in transitional (TS) and follicular (FO) B cells were found in FL-/-mice, and increased frequencies, but not absolute numbers, of marginal zone (MZ) B cells. BAFF-R expression on splenic B cells and serum levels of B cell activating factor (BAFF) was comparable to wildtype (WT) mice. Mixed BM chimeras revealed that the reductions in TS and FO B cells were cell extrinsic. FL administration into FL-/-mice restored the deficiency in TS B cells and normalized the MZ compartment. Ki67 analysis revealed a significant decrease in the proliferative capacity of TS B cells in FL-/-mice. A Bcl2 transgene did not rescue TS cells in FL-/-mice, uncoupling FL-deficiency to Bcl2-dependent survival pathways. Upregulation of CD1d expression and adoptive transfer experiments suggested MZ skewing in FL-/-mice. These findings support an integral role for Flt3 signaling in peripheral B cell maturation.

Original languageEnglish (US)
Pages (from-to)103-117
Number of pages15
JournalImmunity Inflammation and Disease
Volume3
Issue number2
DOIs
StatePublished - Jan 1 2015

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Keywords

  • B cell maturation
  • B lymphopoiesis
  • BAFF
  • Flt3 signaling
  • Follicular B cells
  • Marginal zone B cells
  • Proliferation
  • Transitional B cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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