Interactions between c-kit and stem cell factor are not required for B-cell development in vivo.
The receptor-type tyrosine kinase, c-kit is expressed in hematopoietic stem cells (HSC), myeloid, and lymphoid precursors. In c-kit ligand-deficient mice, absolute numbers of HSC are mildly reduced suggesting that c-kit is not essential for HSC development. However, c-kit- HSC cannot form spleen colonies or reconstitute hematopoietic functions in lethally irradiated recipient mice. Based on in in vitro experiments, a critical role of c-kit in B-cell development was suggested. Here we have investigated the B-cell development of c-kit-null mutant (W/W) mice in vivo. Furthermore, day 13 fetal liver cells from wild type or W/W mice were transferred into immunodeficient RAG-2-/- mice. Surprisingly, transferred c-kit- cells gave rise to all stages of immature B cells in the bone marrow and subsequently to mature conventional B2, as well as B1, type B cells in the recipients to the same extent as transferred wild type cells. Hence, in contrast to important roles of c-kit in the expansion of HSC and the generation of erythroid and myeloid lineages and T-cell precursors, c-kit- HSC can colonize the recipient bone marrow and differentiate into B cells in the absence of c-kit.
Takeda
S
S
Basel Institute for Immunology, Switzerland.
Shimizu
T
T
Rodewald
H R
HR
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*
D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit