title: Impaired B cell development in the absence of Krüppel-like factor 3.
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.
authors: School of Molecular Bioscience, University of Sydney, Sydney, New South Wales 2006, Australia.
authors: Thi Thanh
authors: TT
authors: Vu
authors: Dominique
authors: D
authors: Gatto
authors: Vivian
authors: V
authors: Turner
authors: Alister P W
authors: AP
authors: Funnell
authors: Ka Sin
authors: KS
authors: Mak
authors: Laura J
authors: LJ
authors: Norton
authors: Warren
authors: W
authors: Kaplan
authors: Mark J
authors: MJ
authors: Cowley
authors: Fabien
authors: F
authors: Agenès
authors: Jörg
authors: J
authors: Kirberg
authors: Robert
authors: R
authors: Brink
authors: Richard C M
authors: RC
authors: Pearson
authors: Merlin
authors: M
authors: Crossley
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency* / Q000235:genetics*; D038041:Lymphopoiesis / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010537:Peritoneum / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: C529780:Klf3 protein, mouse; D051741:Kruppel-Like Transcription Factors