Making a Notch in the lymphocyte kit.
The receptor tyrosine kinase c-Kit plays crucial roles in lymphocyte development but there is little information on the molecular circuitry enforcing c-Kit expression. In addition to growth factors, Notch signaling is essential for T cell development. In this issue of the European Journal of Immunology, evidence is provided for an interesting link between c-Kit and Notch. The primary 'test subjects' were a Pax5-deficient 'pro-B cell' line, blocked in its B cell potential, and its non-mutated counterpart, a bone marrow-derived early progenitor with lymphoid and myeloid potential (EPLM). Similar to common lymphoid progenitors, EPLM have a 'B cell-biased' potential, yet show multipotency under appropriate conditions. Following Notch signaling, c-Kit expression was very rapidly upregulated and the development into T cells was found to be c-Kit-dependent. In the absence of Notch signals, c-Kit expression remained low. Development into non-T cell fates (NK or myeloid) was found to be c-Kit-independent. It remains to be determined whether c-Kit is a 'direct' target of the Notch signal transduction pathway; however, these findings, together with those of others, strongly suggest that Notch can contribute to the proper cytokine receptor pattern required for commitment and expansion of early intrathymic progenitors.
Rodewald
Hans-Reimer
HR
Dept. for Immunology, University of Ulm, Ulm, Germany. hans-reimer.rodewald@uni-ulm.de
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001549:Benzamides; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology; D000068877:Imatinib Mesylate; D015851:Interleukin-7 / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology*; D011743:Pyrimidines / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D051880:Receptors, Notch / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001549:Benzamides; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D015851:Interleukin-7; D010879:Piperazines; D011743:Pyrimidines; D015375:Receptors, Interleukin-2; D051880:Receptors, Notch; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit