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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2297-2304.
Prepublished online as a Blood First Edition Paper on June 19, 2008; DOI 10.1182/blood-2008-04-150508.
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Submitted April 8, 2008
Accepted June 3, 2008
FLT3 ligand and not TSLP is the key regulator of IL-7-independent B-1 and B-2 B Lymphopoiesis
Christina T Jensen, Shabnam Kharazi, Charlotta Boiers, Min Cheng, Anna Lubking, Ewa Sitnicka, and Sten Eirik W Jacobsen*
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund, Sweden
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, United Kingdom
* Corresponding author; email: sten.jacobsen{at}imm.ox.ac.uk.
Phenotypically and functionally distinct progenitors and developmental pathways have been proposed to exist for fetally-derived B-1 and conventional B-2 cells. Although IL-7 appears to be the primary regulator of fetal and adult B lymphopoiesis in mice, considerable fetal B lymphopoiesis and postnatal B-cells are sustained in the absence of IL-7, and in man B-cell generation is suggested to be largely or entirely IL-7-independent, as severe combined immune-deficient patients with IL-7-deficiency appear to have normal B-cell numbers. However, the role of other cytokines in IL-7-independent B lymphopoiesis remains to be established. Although thymic stromal lymphopoietin (TSLP) has been proposed to be the main factor driving IL-7-independent B lymphopoiesis, and to distinguish fetal from adult B-cell progenitor development in mice, recent studies failed to support a primary role of TSLP in IL-7-independent fetal B-cell development. However, the role of TSLP in IL-7-independent adult B lymphopoiesis and in particular in regulation of B-1 cells remains to be established. Herein, we demonstrate that rather than TSLP, IL-7 and FLT3 ligand (FLT3L) are combined responsible for all B-cell generation in mice, including recently identified B-1-specified cell progenitors. Thus, the same IL-7 and FLT3L-mediated signaling regulate alternative cellular pathways of fetal and adult B-1 and B-2 B lymphopoiesis.
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