B-Cell Progenitors and Precursors Change Their Microenvironment in Fetal Liver During Early Development

Authors

  • Motokazu Tsuneto,

    Corresponding author
    1. Lymphocyte Development Group, Max Planck Institute for Infection Biology, Berlin, Germany
    • Lymphocyte Development Group, Max Planck Institute for Infection Biology, Charitéplatz 1, D-10117 Berlin, GermanyLymphocyte Development Group, Max Planck Institute for Infection Biology, Charitéplatz 1, D-10117, Berlin, Germany. E-mail: tsuneto@mpiib-berlin.mpg.de melchers@mpiib-berlin.mpg.de Telephone: +49-30-2846-0231; Fax: +49-30-2846-0269

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  • Koji Tokoyoda,

    1. German Rheumatism Research Center (DRFZ), A Leibniz Institute, Berlin, Germany
    2. Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan
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  • Ekaterina Kajikhina,

    1. Lymphocyte Development Group, Max Planck Institute for Infection Biology, Berlin, Germany
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  • Anja E. Hauser,

    1. German Rheumatism Research Center (DRFZ), A Leibniz Institute, Berlin, Germany
    2. Charité Universitätsmedizin, Berlin, Germany
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  • Takahiro Hara,

    1. Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan
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  • Shizue Tani-ichi,

    1. Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan
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  • Koichi Ikuta,

    1. Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan
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  • Fritz Melchers

    Corresponding author
    1. Lymphocyte Development Group, Max Planck Institute for Infection Biology, Berlin, Germany
    • Lymphocyte Development Group, Max Planck Institute for Infection Biology, Charitéplatz 1, D-10117 Berlin, GermanyLymphocyte Development Group, Max Planck Institute for Infection Biology, Charitéplatz 1, D-10117, Berlin, Germany. E-mail: tsuneto@mpiib-berlin.mpg.de melchers@mpiib-berlin.mpg.de Telephone: +49-30-2846-0231; Fax: +49-30-2846-0269

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  • Author contributions: M.T.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; K.T.: conception and design; E.K.: assembly of data; A.H., T.H., S.T., and K.I.: provision of study material or patients; F.M.: conception and design, data analysis and interpretation, and manuscript writing.

Abstract

The microenvironments, in which B lymphocytes develop in fetal liver, are largely still unknown. Among the nonhematopoietic cells, we have identified and FACS-separated two subpopulations, CD45TER119VCAM-1+ cells that are either CD105highLYVE-1high or CD105lowALCAMhigh. Immunohistochemical analyses find three of four c-Kit+IL-7Rα+B220lowCD19SLC B progenitors in contact with vascular endothelial-type LYVE-1high cells on embryonic day 13.5. One day later c-Kit+IL-7Rα+ cells develop to CD19− and +, SLC-expressing, DHJH-rearranged pre/pro and pro/preB-I cells. Less than 10% are still in contact with LYVE-1high cells, but half of them are now in contact with mesenchymally derived ALCAMhigh liver cells. All of these ALCAMhigh cells, but not the LYVE-1high cells produce IL-7 and CXCL12, while both produce CXCL10. Progenitors and pro/preB-I cells are chemoattracted in vitro toward CXCL10 and 12, suggesting that lymphoid progenitors with Ig gene loci in germline configuration enter the developing fetal liver at E13.5 from vascular endothelium, attracted by CXCL10, and then migrate within a day to an ALCAMhigh liver cell microenvironment, differentiating to DHJH-rearranging, surrogate light chain-expressing pre/proB and pro/preB-I cells, attracted by CXCL10 and 12. Between E15.5 and E16.5 preB-I cells expand 10-fold in continued contact with ALCAMhigh cells and begin VH- to DHJH-rearrangements in further differentiated c-KitIL-7Rα preBII cells. STEM Cells 2013;31:2800–2812

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