Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision

Hua Han, Kenji Tanigaki, Norio Yamamoto, Kazuki Kuroda, Momoko Yoshimoto, Tatsutoshi Nakahata, Koichi Ikuta, Tasuku Honjo

Research output: Contribution to journalArticle

419 Citations (Scopus)

Abstract

The transcription factor recombination signal binding protein-J (RBP-J) functions immediately downstream of the cell surface receptor Notch and mediates transcriptional activation by the intracellular domain of all four kinds of Notch receptors. To investigate the function of RBP-J, we introduced loxP sites on both sides of the RBP-J exons encoding its DNA binding domain. Mice bearing the loxP-flanked RBP-J alleles, RBP-Jf/f, were mated with Mx-Cre transgenic mice and deletional mutation of the RBP-J gene in adult mice was induced by injection of the IFN-α inducer poly(I)-poly(C). Here we show that inactivation of RBP-J in bone marrow resulted in a block of T cell development at the earliest stage and increase of B cell development in the thymus. Lymphoid progenitors deficient in RBP-J differentiate into B but not T cells when cultured in 2′-deoxyguanosine-treated fetal thymic lobes by hanging-drop fetal thymus organ culture. Competitive repopulation assay also revealed cell autonomous deficiency of T cell development from bone marrow of RBP-J knockout mouse. Myeloid and B lineage differentiation appears normal in the bone marrow of RBP-J-inactivated mice. These results suggest that RBP-J, probably by mediating Notch signaling, controls T versus B cell fate decision in lymphoid progenitors.

Original languageEnglish (US)
Pages (from-to)637-645
Number of pages9
JournalInternational Immunology
Volume14
Issue number6
StatePublished - 2002
Externally publishedYes

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Immunoglobulin J Recombination Signal Sequence-Binding Protein
Gene Knockout Techniques
Transcription Factors
Bone Marrow
T-Lymphocytes
Thymus Gland
B-Lymphocytes
Poly I
Notch Receptors
Deoxyguanosine
Organ Culture Techniques

Keywords

  • Gene targeting
  • Notch
  • RBP-J
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology

Cite this

Han, H., Tanigaki, K., Yamamoto, N., Kuroda, K., Yoshimoto, M., Nakahata, T., ... Honjo, T. (2002). Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision. International Immunology, 14(6), 637-645.

Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision. / Han, Hua; Tanigaki, Kenji; Yamamoto, Norio; Kuroda, Kazuki; Yoshimoto, Momoko; Nakahata, Tatsutoshi; Ikuta, Koichi; Honjo, Tasuku.

In: International Immunology, Vol. 14, No. 6, 2002, p. 637-645.

Research output: Contribution to journalArticle

Han, H, Tanigaki, K, Yamamoto, N, Kuroda, K, Yoshimoto, M, Nakahata, T, Ikuta, K & Honjo, T 2002, 'Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision', International Immunology, vol. 14, no. 6, pp. 637-645.
Han, Hua ; Tanigaki, Kenji ; Yamamoto, Norio ; Kuroda, Kazuki ; Yoshimoto, Momoko ; Nakahata, Tatsutoshi ; Ikuta, Koichi ; Honjo, Tasuku. / Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision. In: International Immunology. 2002 ; Vol. 14, No. 6. pp. 637-645.
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