Complementary signaling through flt3 and interleukin-7 receptor alpha is indispensable for fetal and adult B cell genesis.
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Journal of Experimental Medicine |
Volume | 198 |
Issue number | 10 |
Pages (from-to) | 1495-506 |
Number of pages | 11 |
ISSN | 0022-1007 |
DOIs | |
Publication status | Published - 2003 |
Bibliographical note
Keywords: Animals; B-Lymphocytes; Cell Differentiation; Membrane Proteins; Mice; Mice, Knockout; Peyer's Patches; Receptors, Interleukin-7; Signal Transduction
ID: 5141295