Thymic stromal lymphopoietin induces early human B-cell proliferation and differentiation.
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.
Scheeren
Ferenc A
FA
Division of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
van Lent
Anja U
AU
Nagasawa
Maho
M
Weijer
Kees
K
Spits
Hergen
H
Legrand
Nicolas
N
Blom
Bianca
B
D001402:B-Lymphocytes / Q000166:cytology*; D001853:Bone Marrow / Q000196:embryology; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000196:embryology; D038041:Lymphopoiesis / Q000187:drug effects; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
C498762:CRLF2 protein, human; D016207:Cytokines; C508605:IL7 protein, human; D015851:Interleukin-7; D018121:Receptors, Cytokine; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; C415350:interleukin-7 receptor, alpha chain; D011505:Protein-Tyrosine Kinases; D000094632:Thymic Stromal Lymphopoietin