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Complementary Signaling through flt3 and Interleukin-7 Receptor {alpha} Is Indispensable for Fetal and Adult B Cell Genesis.

Sitnicka Quinn, Ewa LU ; Brakebusch, Cord; Martensson, Inga-Lill; Svensson Frej, Marcus LU ; Agace, William LU ; Sigvardsson, Mikael LU ; Buza-Vidas, Natalija LU ; Bryder, David LU ; M Cilio, Corrado and Ahlenius, Henrik LU , et al. (2003) In Journal of Experimental Medicine 198(10). p.1495-1506
Abstract
Extensive studies of mice deficient in one or several cytokine receptors have failed to support an indispensable role of cytokines in development of multiple blood cell lineages. Whereas B1 B cells and Igs are sustained at normal levels throughout life of mice deficient in IL-7, IL-7R{alpha}, common cytokine receptor gamma chain, or flt3 ligand (FL), we report here that adult mice double deficient in IL-7R{alpha} and FL completely lack visible LNs, conventional IgM+ B cells, IgA+ plasma cells, and B1 cells, and consequently produce no Igs. All stages of committed B cell progenitors are undetectable in FL-/- x IL-7R{alpha}-/- BM that also lacks expression of the B cell commitment factor Pax5 and its direct target genes. Furthermore, in... (More)
Extensive studies of mice deficient in one or several cytokine receptors have failed to support an indispensable role of cytokines in development of multiple blood cell lineages. Whereas B1 B cells and Igs are sustained at normal levels throughout life of mice deficient in IL-7, IL-7R{alpha}, common cytokine receptor gamma chain, or flt3 ligand (FL), we report here that adult mice double deficient in IL-7R{alpha} and FL completely lack visible LNs, conventional IgM+ B cells, IgA+ plasma cells, and B1 cells, and consequently produce no Igs. All stages of committed B cell progenitors are undetectable in FL-/- x IL-7R{alpha}-/- BM that also lacks expression of the B cell commitment factor Pax5 and its direct target genes. Furthermore, in contrast to IL-7R{alpha}-/- mice, FL-/- x IL-7R{alpha}-/- mice also lack mature B cells and detectable committed B cell progenitors during fetal development. Thus, signaling through the cytokine tyrosine kinase receptor flt3 and IL-7R{alpha} are indispensable for fetal and adult B cell development. (Less)
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keywords
IL-7 receptor, Flt3 ligand, B1 cells, Pax5, lymphopoiesis
in
Journal of Experimental Medicine
volume
198
issue
10
pages
1495 - 1506
publisher
Rockefeller University Press
external identifiers
  • wos:000186845600005
  • pmid:14610045
  • scopus:10744221710
ISSN
1540-9538
DOI
10.1084/jem.20031152
language
English
LU publication?
yes
id
193b69e0-16b1-430d-b052-504abf5e6466 (old id 119047)
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2007-06-26 12:49:54
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2017-01-01 07:26:59
@article{193b69e0-16b1-430d-b052-504abf5e6466,
  abstract     = {Extensive studies of mice deficient in one or several cytokine receptors have failed to support an indispensable role of cytokines in development of multiple blood cell lineages. Whereas B1 B cells and Igs are sustained at normal levels throughout life of mice deficient in IL-7, IL-7R{alpha}, common cytokine receptor gamma chain, or flt3 ligand (FL), we report here that adult mice double deficient in IL-7R{alpha} and FL completely lack visible LNs, conventional IgM+ B cells, IgA+ plasma cells, and B1 cells, and consequently produce no Igs. All stages of committed B cell progenitors are undetectable in FL-/- x IL-7R{alpha}-/- BM that also lacks expression of the B cell commitment factor Pax5 and its direct target genes. Furthermore, in contrast to IL-7R{alpha}-/- mice, FL-/- x IL-7R{alpha}-/- mice also lack mature B cells and detectable committed B cell progenitors during fetal development. Thus, signaling through the cytokine tyrosine kinase receptor flt3 and IL-7R{alpha} are indispensable for fetal and adult B cell development.},
  author       = {Sitnicka Quinn, Ewa and Brakebusch, Cord and Martensson, Inga-Lill and Svensson Frej, Marcus and Agace, William and Sigvardsson, Mikael and Buza-Vidas, Natalija and Bryder, David and M Cilio, Corrado and Ahlenius, Henrik and Maraskovsky, Eugene and Peschon, Jacques J. and Jacobsen, Sten Eirik W.},
  issn         = {1540-9538},
  keyword      = {IL-7 receptor,Flt3 ligand,B1 cells,Pax5,lymphopoiesis},
  language     = {eng},
  number       = {10},
  pages        = {1495--1506},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Complementary Signaling through flt3 and Interleukin-7 Receptor {alpha} Is Indispensable for Fetal and Adult B Cell Genesis.},
  url          = {http://dx.doi.org/10.1084/jem.20031152},
  volume       = {198},
  year         = {2003},
}