FLT3 ligand and not TSLP is the key regulator of IL-7-independent B-1 and B-2 B lymphopoiesis.
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 cytokine 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; in humans, B-cell generation is suggested to be largely 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. Here we demonstrate that, rather than TSLP, IL-7 and FLT3 ligand are combined responsible for all B-cell generation in mice, including recently identified B-1-specified cell progenitors. Thus, the same IL-7- and FLT3 ligand-mediated signal-ing regulates alternative pathways of fetal and adult B-1 and B-2 lymphopoiesis.
Jensen
Christina T
CT
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
Kharazi
Shabnam
S
Böiers
Charlotta
C
Cheng
Min
M
Lübking
Anna
A
Sitnicka
Ewa
E
Jacobsen
Sten Eirik W
SE
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D019070:Cell Lineage; D016207:Cytokines / Q000502:physiology*; D005333:Fetus / Q000166:cytology; D015851:Interleukin-7 / Q000502:physiology*; D038041:Lymphopoiesis; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D015851:Interleukin-7; D008565:Membrane Proteins; C084881:flt3 ligand protein; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse