Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 198, Issue 10, Pages 1495-1506Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20031152
Keywords
lymphopoiesis; IL-7 receptor; Flt3 ligand; Pax5; B1 cells
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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.
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