Identification of an Essential Cytoplasmic Region of Interleukin-7 Receptor α Subunit in B-Cell Development.

Interleukin-7 (IL-7) is essential for lymphocyte development. To identify the functional subdomains in the cytoplasmic tail of the IL-7 receptor (IL-7R) alpha chain, here, we constructed a series of IL-7R alpha deletion mutants. We found that IL-7R alpha-deficient hematopoietic progenitor cells (HPCs) gave rise to B cells both in vitro and in vivo when a wild-type (WT) IL-7R alpha chain was introduced; however, no B cells were observed under the same conditions from IL-7R alpha-deficient HPCs with introduction of the exogenous IL-7R alpha subunit, which lacked the amino acid region at positions 414-441 (d414-441 mutant). Signal transducer and activator of transcription 5 (STAT5) was phosphorylated in cells with the d414-441 mutant, similar to that in WT cells, in response to IL-7 stimulation. In contrast, more truncated STAT5 (tSTAT5) was generated in cells with the d414-441 mutant than in WT cells. Additionally, the introduction of exogenous tSTAT5 blocked B lymphopoiesis but not myeloid cell development from WT HPCs in vivo. These results suggested that amino acids 414-441 in the IL-7R alpha chain formed a critical subdomain necessary for the supportive roles of IL-7 in B-cell development.