Hepatocyte Nuclear Factor 1A Is a Cell-Intrinsic Transcription Factor Required for B Cell Differentiation and Development in Mice

The Journal of Immunology : Official Journal of the American Association of Immunologists
Karin von Wnuck LipinskiBodo Levkau

Abstract

The hepatocyte NF (HNF) family of transcription factors regulates the complex gene networks involved in lipid, carbohydrate, and protein metabolism. In humans, HNF1A mutations cause maturity onset of diabetes in the young type 3, whereas murine HNF6 participates in fetal liver B lymphopoiesis. In this study, we have identified a crucial role for the prototypical member of the family HNF1A in adult bone marrow B lymphopoiesis. HNF1A(-/-) mice exhibited a clear reduction in total blood and splenic B cells and a further pronounced one in transitional B cells. In HNF1A(-/-) bone marrow, all B cell progenitors-from pre-pro-/early pro-B cells to immature B cells-were dramatically reduced and their proliferation rate suppressed. IL-7 administration in vivo failed to boost B cell development in HNF1A(-/-) mice, whereas IL-7 stimulation of HNF1A(-/-) B cell progenitors in vitro revealed a marked impairment in STAT5 phosphorylation. The B cell differentiation potential of HNF1A(-/-) common lymphoid progenitors was severely impaired in vitro, and the expression of the B lymphopoiesis-promoting transcription factors E2A, EBF1, Pax5, and Bach2 was reduced in B cell progenitors in vivo. HNF1A(-/-) bone marrow chimera featured a dramatic defe...Continue Reading

References

Apr 1, 1995·The Journal of Experimental Medicine·U von Freeden-JeffryR Murray
Nov 1, 1994·The Journal of Experimental Medicine·J J PeschonB L Davison
May 5, 1998·Molecular and Cellular Biology·Y H LeeF J Gonzalez
Feb 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·L A GeiselhartK L Komschlies
Mar 1, 2002·Immunity·Rodney P DeKoterHarinder Singh
May 16, 2002·Blood·Terry J Fry, Crystal L Mackall
Aug 14, 2002·Annals of Medicine·Amanda Stride, Andrew T Hattersley
May 30, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alistair J WattStephen A Duncan
Jun 18, 2003·European Journal of Immunology·Shigenari HirokawaAkira Kudo
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Caroline BouzinGuy G Rousseau
Feb 14, 2004·Immunological Reviews·Thomas T SuDavid J Rawlings
Feb 14, 2004·Immunological Reviews·Rita CarsettiHedda Wardmann
Feb 28, 2004·Science·Duncan T OdomRichard A Young
Apr 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine A GoetzMichael A Farrar
Jun 24, 2004·The Journal of Experimental Medicine·Christopher S SeetBarbara L Kee
Oct 8, 2004·Developmental Cell·Kay L MedinaHarinder Singh
Apr 20, 2005·The Journal of Experimental Medicine·Kazu KikuchiMotonari Kondo
Oct 14, 2005·Kidney International·Peter IgarashiThomas Hiesberger
Nov 29, 2005·Molecular Immunology·David G T HessleinDavid G Schatz
Feb 17, 2006·Current Topics in Microbiology and Immunology·K L Medina, H Singh
Feb 24, 2006·Nature Reviews. Immunology·Takashi Nagasawa
Mar 1, 2006·The Journal of Experimental Medicine·Lynn L RumfeltRichard R Hardy
Aug 16, 2006·Cellular and Molecular Life Sciences : CMLS·J R Friedman, K H Kaestner
Nov 15, 2006·Molecular and Cellular Biology·Stephanie RoesslerRudolf Grosschedl
Jun 22, 2007·Immunity·Richard R HardyKenneth Dorshkind
Jun 22, 2007·Immunity·Stephen L Nutt, Barbara L Kee
Aug 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Annaiah CariappaShiv Pillai
Apr 25, 2008·Current Opinion in Immunology·David Allman, Shiv Pillai
Jun 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kazu KikuchiMotonari Kondo
Dec 9, 2008·Nature Genetics·Sekar KathiresanL Adrienne Cupples
Feb 10, 2009·Nature Genetics·Jeanette ErdmannHeribert Schunkert
Dec 31, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Laura PelletierJessica Zucman-Rossi
May 25, 2011·Proceedings of the National Academy of Sciences of the United States of America·Christina ChristoffersenBjörn Dahlbäck

❮ Previous
Next ❯

Citations

Aug 1, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hong GuoAlan D Friedman
Feb 6, 2020·Viruses·Kristi L TurtonTrushar R Patel
Oct 1, 2019·Current Molecular Pharmacology·Sumreen Begum
Nov 5, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexander MuckenhuberWilko Weichert

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B cell Differentiation

Depending on the signal received through the B cell receptor and other receptors, B cells differentiate into follicular or marginal zone B cells. Here is the latest research pertaining to this differentiation process.