Lymphocyte development in neonatal and adult c-Kit-deficient (c-KitW/W) mice.
Hematopoietic stem cells and lymphocyte progenitors express the receptor tyrosine kinase c-Kit. In fetal and neonatal life, c-Kit plays a redundant role in T, and no apparant role in B cell development. In neonatal mice deficient for both c-Kit and the common gamma chain (gammac), a component of the interleukin-7 (IL-7) receptor, the thymus is alymphoid, and therefore lacks T cell receptor (TCR) beta, gamma, and delta rearrangements. Thus, a critical role for c-Kit in T cell development around birth is well established. More recently, it has become possible to examine the impact of c-Kit deficiency under conditions of steady state lymphopoiesis in adult life. Such analysis has been made possible by the identification of a viable adult c-Kit-deficient (c-KitW/W) variant, termed the Vickid mouse. The Vickid mouse arose by outcrossing c-KitW-bearing mice of the WB strain, in which lack of c-Kit is lethal, to a mixed genetic background. In adult Vickid mice, mainstream alphabeta TCR+ thymocyte development, and B cell development in the bone marrow are severely c-Kit-dependent with progressive age. Analysis of other pathways of developing T cells, i.e. CD4-CD8- (double neagative [DN]) alphabeta TCR+ and DN gammadelta TCR+ thymocytes revealed that the development of both lineages is also severely affected by lack of c-Kit. However, numbers of gammadelta TCR+ T cells decline before numbers of alphabeta TCR+ T cells in the thymus. In contrast to T and B cell development, generation of NK cells is not affected in adult c-KitW/W mice.
Waskow
Claudia
C
Dept. for Immunology, University of Ulm, D-89070 Ulm, Germany. claudia.waskow@medizin.uni-ulm.de
Rodewald
Hans-Reimer
HR
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019009:Proto-Oncogene Proteins c-kit