Thymic stromal lymphopoietin induces early human B‐cell proliferation and differentiation

FA Scheeren, AU van Lent… - European journal of …, 2010 - Wiley Online Library
FA Scheeren, AU van Lent, M Nagasawa, K Weijer, H Spits, N Legrand, B Blom
European journal of immunology, 2010Wiley Online Library
Thymic stromal lymphopoietin (TSLP) is a cytokine that binds the IL‐7‐receptor‐α 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 …
Abstract
Thymic stromal lymphopoietin (TSLP) is a cytokine that binds the IL‐7‐receptor‐α 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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