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  • Title: Thymic stromal lymphopoietin induces early human B-cell proliferation and differentiation.
    Author: Scheeren FA, van Lent AU, Nagasawa M, Weijer K, Spits H, Legrand N, Blom B.
    Journal: Eur J Immunol; 2010 Apr; 40(4):955-65. PubMed ID: 20127673.
    Abstract:
    Thymic stromal lymphopoietin (TSLP) is a cytokine that binds the IL-7-receptor-alpha chain and a unique TSLP receptor (TSLPR) chain. The role of TSLP in human B-cell development has not been elucidated. We show that TSLPR transcripts are expressed most prominently in CD34(+) cells from fetal liver and BM. In general, cell surface expression of TSLPR was low, except on a subset of multilineage-commited progenitor cells. TSLP induced the tyrosine-phosphorylation of STAT5 and the proliferation of multilineage-commited progenitor cells, pro-B cells and pre-B cells. Compared with IL-7, the levels of proliferation after stimulation of the B-cell progenitors with TSLP were lower. Expression of the BCR on the cell surface of fetal cells was inversely correlated to TSLP or IL-7 responsiveness. Pre-B cells from fetal BM, but not fetal liver, were refractory to TSLP or IL-7 stimulation. When employing an in vitro B-cell differentiation culture system starting from CD34(+)CD38(-) multipotent HSC, IL-7 induced a short wave of precursor cell expansion but did not result in long-term survival of mature B cells. TSLP was capable of increasing the proportion and the absolute numbers of more mature human B cells. Overall, we provide evidence that TSLP supports human B-cell differentiation from fetal hematopoietic progenitors.
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