Stat5 is essential for early B cell development but not for B cell maturation and function.
The two closely related Stat5 (Stat5A and Stat5B) proteins are activated by a broad spectrum of cytokines. However, with the complication of the involvement of Stat5A/5B in stem cell function, the role of Stat5A/5B in the development and function of lymphocytes, especially B cells, is not fully understood. In this study, we demonstrated that Stat5A/5B(-/-) fetal liver cells had severe diminution of B cell progenitors but clearly had myeloid progenitors. Consistently, the mutant fetal liver cells could give rise to hemopoietic progenitors and myeloid cells but not B cells beyond pro-B cell progenitors in lethally irradiated wild-type or Jak3(-/-) mice. Deletion of Stat5A/5B in vitro directly impaired IL-7-mediated B cell expansion. Of note, reintroduction of Stat5A back into Stat5A/5B(-/-) fetal liver cells restored their abilities to develop B cells. Importantly, CD19-Cre-mediated deletion of Stat5A/5B in the B cell compartment specifically impaired early B cell development but not late B cell maturation. Moreover, the B cell-specific deletion of Stat5A/5B did not impair splenic B cell survival, proliferation, and Ig production. Taken together, these data demonstrate that Stat5A/5B directly control IL-7-mediated early B cell development but are not required for B cell maturation and Ig production.
Dai
Xuezhi
X
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People's Republic of China.
Chen
Yuhong
Y
Di
Lie
L
Podd
Andrew
A
Li
Geqiang
G
Bunting
Kevin D
KD
Hennighausen
Lothar
L
Wen
Renren
R
Wang
Demin
D
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000276:immunology / Q000378:metabolism*
D015851:Interleukin-7; D050799:STAT5 Transcription Factor