Interleukin-7R alpha mRNA expression increases as stem cells differentiate into T and B lymphocyte progenitors

The gamma common (gamma c) chain is a partner in several interleukin receptor complexes, including the interleukin-2 receptor (IL-2R), IL-4R, and IL-7R. Mutations in the gamma c gene are associated with X-linked severe combined immunodeficiency (SCID). Using reverse transcriptase-PCR, we examined the level of mRNA-encoding gamma c and its partners in mouse pluripotent hematopoietic stem cells (PHSCs), which repopulate both bone marrow and thymus. We also assayed developing lymphocytes to define which, if any, IL-R complexes are expressed at the earliest stage of T and B lymphocyte maturation. RNA extracted from bone marrow-derived PHSCs did not contain detectable levels of mRNA-encoding IL-7R alpha. However, the most primitive (CD4- CD8-) T cells from the thymus and the most primitive (c-kit+ B220+) B cells from bone marrow contained high levels of IL-7R alpha mRNA. There were no detectable differences between PHSCs and primitive or more mature T and B cells for expression of gamma c mRNA. We conclude that the onset of IL-7R formation occurs at the earliest stage of differentiation of T and B lymphocytes. Our findings are consistent with the hypothesis that the absence of an intact IL-7R (IL-7R alpha and gamma c) may be a critical loss that interrupts lymphopoiesis.