STAT3 positively regulates an early step in B-cell development.
Transcription factors are critical for instructing the development of B lymphocytes from multipotential progenitor cells in the bone marrow (BM). Here, we show that the absence of STAT3 impaired B-cell development. Mice selectively lacking STAT3 in BM progenitor cells displayed reduced numbers of mature B cells, both in the BM and in the periphery. The reduction in the B-cell compartment included reduced percentages and numbers of pro-B, pre-B, and immature B cells in the absence of STAT3, whereas the number of pre-pro-B cells was increased. We found that pro-B and pre-B-cell populations lacking STAT3 were hyporesponsive to IL-7 because of a decreased number of IL-7-responsive cells rather than decreased expression or signaling of IL-7Ralpha. Moreover, STAT3-deficient mice displayed enhanced apoptosis in the pro-B population when deprived of survival factors, suggesting that at least 2 mechanisms (impaired differentiation and enhanced apoptosis) are involved in the mutant phenotype. Last, BM transplantation confirmed that impaired B lymphopoiesis in the absence of STAT3 was caused by a cell autonomous defect. In sum, these studies defined a specific role for STAT3 in early B-cell development, probably acting at the pre-pro-B transition by contributing to the survival of IL-7-responsive progenitors.
Chou
Wei-Chun
WC
Graduate Institute of Immunology, National Taiwan University College of Medicine, Rm 513, No. 1, Jen-Ai Road, Section 1, Taipei, 100 Taiwan.
Levy
David E
DE
Lee
Chien-Kuo
CK
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D017931:DNA Primers; D005838:Genotype; D015851:Interleukin-7 / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D017931:DNA Primers; D015851:Interleukin-7; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse