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* State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People’s Republic of China;
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226;
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106;
Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; and
¶ Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by National Institutes of Health Grants R01 DK059380 (to K.D.B.), R01 AI52327 (to R.W.), R01 HL073284 (to D.W.), and by American Cancer Society Grant RSG CCG-106204 (to D.W.).
2 Address correspondence and reprint requests to Dr. Demin Wang, Blood Research Institute, 8727 Watertown Plank Road, Milwaukee, WI 53226. E-mail address: demin.wang{at}bcw.edu
3 Abbreviations used in this paper: BM, bone marrow; T1, transitional B cells of type 1; T2, transitional B cells of type 2; FO, follicular; IRES, internal ribosome entry site; MSCV, murine stem cell promoter; SCF, stem cell factor.
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