title: Complementary signaling through flt3 and interleukin-7 receptor alpha is indispensable for fetal and adult B cell genesis.
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-7Ralpha, common cytokine receptor gamma chain, or flt3 ligand (FL), we report here that adult mice double deficient in IL-7Ralpha 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-7Ralpha-/- BM that also lacks expression of the B cell commitment factor Pax5 and its direct target genes. Furthermore, in contrast to IL-7Ralpha-/- mice, FL-/- x IL-7Ralpha-/- 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-7Ralpha are indispensable for fetal and adult B cell development.
authors: Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University Hospital, BMC 10, Klinikgatan 26, 221-84 Lund, Sweden.
authors: Ewa
authors: E
authors: Sitnicka
authors: Cord
authors: C
authors: Brakebusch
authors: Inga-Lill
authors: IL
authors: Martensson
authors: Marcus
authors: M
authors: Svensson
authors: William W
authors: WW
authors: Agace
authors: Mikael
authors: M
authors: Sigvardsson
authors: Natalija
authors: N
authors: Buza-Vidas
authors: David
authors: D
authors: Bryder
authors: Corrado M
authors: CM
authors: Cilio
authors: Henrik
authors: H
authors: Ahlenius
authors: Eugene
authors: E
authors: Maraskovsky
authors: Jacques J
authors: JJ
authors: Peschon
authors: Sten Eirik W
authors: SE
authors: Jacobsen
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D020395:Receptors, Interleukin-7; C084881:flt3 ligand protein; C415350:interleukin-7 receptor, alpha chain