Impaired B cell development in the absence of Krüppel-like factor 3

Thi Thanh Vu, Dominique Gatto, Vivian Turner, Alister P W Funnell, Ka Sin Mak, Laura J Norton, Warren Kaplan, Mark J Cowley, Fabien Agenès, Jörg Kirberg, Robert Brink, Richard C M Pearson, Merlin Crossley

Research output: Contribution to journalArticlepeer-review

Abstract

Krüppel-like factor 3 (Klf3) is a member of the Klf family of transcription factors. Klfs are widely expressed and have diverse roles in development and differentiation. In this study, we examine the function of Klf3 in B cell development by studying B lymphopoiesis in a Klf3 knockout mouse model. We show that B cell differentiation is significantly impaired in the bone marrow, spleen, and peritoneal cavity of Klf3 null mice and confirm that the defects are cell autonomous. In the bone marrow, there is a reduction in immature B cells, whereas recirculating mature cells are noticeably increased. Immunohistology of the spleen reveals a poorly structured marginal zone (MZ) that may in part be caused by deregulation of adhesion molecules on MZ B cells. In the peritoneal cavity, there are significant defects in B1 B cell development. We also report that the loss of Klf3 in MZ B cells is associated with reduced BCR signaling strength and an impaired ability to respond to LPS stimulation. Finally, we show increased expression of a number of Klf genes in Klf3 null B cells, suggesting that a Klf regulatory network may exist in B cells.

Original languageEnglish
Pages (from-to)5032-42
Number of pages11
JournalJournal of Immunology
Volume187
Issue number10
DOIs
Publication statusPublished - 15 Nov 2011
Externally publishedYes

Keywords

  • Animals
  • B-Lymphocyte Subsets
  • Bone Marrow Cells
  • Cell Differentiation
  • Kruppel-Like Transcription Factors
  • Lymphopoiesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peritoneum
  • Radiation Chimera
  • Spleen

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