Complementary signaling through flt3 and interleukin-7 receptor alpha is indispensable for fetal and adult B cell genesis.
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.
Sitnicka
Ewa
E
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.
Brakebusch
Cord
C
Martensson
Inga-Lill
IL
Svensson
Marcus
M
Agace
William W
WW
Sigvardsson
Mikael
M
Buza-Vidas
Natalija
N
Bryder
David
D
Cilio
Corrado M
CM
Ahlenius
Henrik
H
Maraskovsky
Eugene
E
Peschon
Jacques J
JJ
Jacobsen
Sten Eirik W
SE
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
D008565:Membrane Proteins; D020395:Receptors, Interleukin-7; C084881:flt3 ligand protein; C415350:interleukin-7 receptor, alpha chain