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Thymic stromal-derived lymphopoietin distinguishes fetal from adult B cell development

Nature Immunology volume 4, pages 773–779 (2003)Cite this article

Abstract

Deletions of interleukin 7 (IL-7) or its receptor components permit fetal but not adult B cell development in mice. Mice deficient in IL-7 receptor α (IL-7Rα) had 1% the number of B cells of controls and 10% that of mice deficient in the common γ chain. As IL-7Rα is also a receptor for thymic stromal-derived lymphopoietin (TSLP), we assayed the ability of TSLP to support proliferation of fetal or adult precursor B cells. Only fetal-derived pro-B cells were able to respond to TSLP, although pre-B cells from both origins were TSLP-responsive. Fetal but not adult precursors generated a measurable B cell compartment in the absence of IL-7. The residual B cells found in IL-7Rα-deficient mice required fetal liver kinase 2 (Flk-2) for their development. Thus, IL-7Rα- and Flk-2-mediated signals account for the generation of almost all mouse B lymphocytes.

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Figure 1: Splenic B cells in T, γT, 7RT, and γ7RT mice.
Figure 2: B cell development in T, γT, 7RT and γ7RT mice.
Figure 3: Fetal liver, but not bone marrow precursors, generate B cells in the absence of IL-7.
Figure 4: TSLP is selectively active on pro-B cells derived from fetal liver, but not adult bone marrow.
Figure 5: TSLP and IL-7 drive differentiation of IgM+ cells in wild-type pro-B cell cultures, but only TSLP supports the proliferation of γc− fetal liver pro-B cells.
Figure 6: Pro-B lymphocytes from fetal liver and bone marrow express similar amounts of TSLPR, IL-7Rα and γc.
Figure 7: Absence of B lymphocytes in Il7ra−/−Flk2−/− mice.

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Acknowledgements

We wish to thank J.P. Pereira for providing cDNA to set up the Tslpr PCR; B. Hampel for reagents; L. Boucontet for assistance with TaqMan; I. Lemischka for Flk-2-deficient mice; and F. Colucci, M. Garcia-Ojeda and S. Dias for critical reading of the manuscript. This work was supported by the Institut Pasteur, the Land Nordrhein-Westfalen, grants from the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, Förderkennzeichen 01 KS 9502 (ZMMK,Cologne) to Klaus Rajewsky and W.M., the Association pour la Recherché contre le Cancer, the Institut Nationale de la Santè et Recherche Medicale, and the Ligue Nationale Contre Le Cancer as an Associated Laboratory. C.V. was supported by fellowships from the Fondation pour la Recherche Medicale and the Institut Nationale de la Santè et Recherche Medicale (INSERM).

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Authors and Affiliations

  1. Unité des Cytokines et Développement Lymphoïde, INSERM Equipe, 101 Institut Pasteur, Paris, 75724, France

    Christian A J Voßhenrich & James P Di Santo

  2. Institute for Genetics, University of Cologne, Cologne, 50931, Germany

    Christian A J Voßhenrich & Werner Müller

  3. Unité du Développement des Lymphocytes, CNRS URA 1961, Institut Pasteur, Paris, 75724, France

    Ana Cumano & Paulo Vieira

  4. Department of Experimental Immunology, GBF, Braunschweig, 38124, Germany

    Werner Müller

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  1. Christian A J Voßhenrich
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Correspondence to Paulo Vieira.

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Voßhenrich, C., Cumano, A., Müller, W. et al. Thymic stromal-derived lymphopoietin distinguishes fetal from adult B cell development. Nat Immunol 4, 773–779 (2003). https://doi.org/10.1038/ni956

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