Making a Notch in the lymphocyte kit

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Abstract
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.See accompanying article: http://dx.doi.org/10.1002/eji.200535760