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Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors

Nature volume 401, pages 603–606 (1999)Cite this article

Abstract

The mechanisms controlling the commitment of haematopoietic progenitors to the B-lymphoid lineage are poorly understood. The observations that mice deficient in E2A1,2 and EBF3 lack B-lineage cells have implicated these two transcription factors in the commitment process. Moreover, the expression of genes encoding components of the rearrangement machinery (RAG1, RAG2, TdT) or pre-B-cell receptor (λ5, VpreB, Igα, Igβ) has been considered to indicate B-lineage commitment4. All these genes including E2A and EBF are expressed in pro-B cells lacking the transcription factor Pax5 (refs 5,6,7). Here we show that cloned Pax5-deficient pro-B cells transferred into RAG2-deficient mice provide long-term reconstitution of the thymus and give rise to mature T cells expressing α/β-T-cell receptors. The bone marrow of these mice contains a population of cells of Pax5-/- origin with the same phenotype as the donor pro-B cells. When transferred into secondary recipients, these pro-B cells again home to the bone marrow and reconstitute the thymus. Hence, B-lineage commitment is determined neither by immunoglobulin DJ rearrangement nor by the expression of E2A, EBF, λ5, VpreB, Igα and Igβ. Instead, our data implicate Pax5 in the control of B-lineage commitment.

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Figure 1: Reconstitution of T-cell development by Pax5-/- pro-B cells.
Figure 2: Gene expression and rearrangement in thymocytes derived from Pax5-/- pro-B cells.
Figure 3: Time course of thymus reconstitution.
Figure 4: Homing and self-renewal of Pax5-/- pro-B cells in the bone marrow.

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Acknowledgements

We thank J. Andersson, K. Karjalainen and E. Palmer for critical reading of the manuscript; A. Groenewegen, N. Straube, M. Dessing and A. Pickert for technical assistance; E. Wagner for animal husbandry; and T. Winkler for the GFP retrovirus. This work was supported by the Basel Institute for Immunology, the I.M.P. Vienna and a grant from the Austrian Industrial Research Promotion Fund. The Basel Institute for Immunology was founded and is supported by F. Hoffmann-La Roche Ltd., Basel, Switzerland.

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  1. Stephen L. Nutt

    Present address: Wellcome/CRC Institute, Tennis Court Road, Cambridge, CB2 1QR, UK

Authors and Affiliations

  1. Basel Institute for Immunology, Grenzacherstrasse 487, Basel, CH-4005, Switzerland

    Antonius G. Rolink & Fritz Melchers

  2. Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, Vienna, A-1030, Austria

    Stephen L. Nutt & Meinrad Busslinger

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  1. Antonius G. Rolink
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Correspondence to Antonius G. Rolink.

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Rolink, A., Nutt, S., Melchers, F. et al. Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors. Nature 401, 603–606 (1999). https://doi.org/10.1038/44164

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