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Int J Mol Sci. 2018 Aug 25;19(9). pii: E2522. doi: 10.3390/ijms19092522.

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

Author information

1
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. hirotake.kasai@yamanashi.ac.jp.
2
Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan. kuwabara@med.toho-u.ac.jp.
3
Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan. ym04083@yahoo.co.jp.
4
Toho University Graduate School of Medicine, Tokyo 143-8540, Japan. ym04083@yahoo.co.jp.
5
Department of Urology, Toho University Omori Medical Center, Tokyo 143-8541, Japan. ym04083@yahoo.co.jp.
6
Department of Urology, Toho University Omori Medical Center, Tokyo 143-8541, Japan. koichin@med.toho-u.ac.jp.
7
Department of Molecular Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan. motonari.kondo@med.toho-u.ac.jp.

Abstract

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) α chain, here, we constructed a series of IL-7Rα deletion mutants. We found that IL-7Rα-deficient hematopoietic progenitor cells (HPCs) gave rise to B cells both in vitro and in vivo when a wild-type (WT) IL-7Rα chain was introduced; however, no B cells were observed under the same conditions from IL-7Rα-deficient HPCs with introduction of the exogenous IL-7Rα 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-7Rα chain formed a critical subdomain necessary for the supportive roles of IL-7 in B-cell development.

KEYWORDS:

B-cell development; interleukin-7; interleukin-7 receptor; signal transducer and activator of transcription 5

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