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Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool

Author

Listed:
  • Yan-Feng Li

    (Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research)

  • Shengli Xu

    (Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Xijun Ou

    (Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research)

  • Kong-Peng Lam

    (Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research
    Yong Loo Lin School of Medicine, National University of Singapore
    Yong Loo Lin School of Medicine, National University of Singapore
    Yong Loo Lin School of Medicine, National University of Singapore)

Abstract

Germline or B-cell-specific loss of Ptpn6 gene encoding the Shp1 protein tyrosine phosphatase leads to skewed B lymphopoiesis and systemic autoimmunity. Here, to study its role in B-cell terminal differentiation, we generated Ptpn6f/fAicdaCre/+ mice with Shp1 ablated only in activated B cells. We show that Ptpn6f/fAicdaCre/+ mice have normal B-cell development but exhibit defective class-switched primary and recalled antibody response to a T-cell-dependent antigen. Germinal centres are present but do not persist and memory B cells are not formed. Interestingly, Shp1-deficient plasma cells are generated in the spleen but do not contribute to the bone marrow long-lived pool. Plasma cells lacking Shp1 exhibit aberrant α4β1 integrin activation due to dysregulated Src- and PI3-kinase signalling and manifest attenuated migration in vitro and defective bone marrow homing when reconstituted in vivo. Interrupting α4β1–VCAM-1 interaction rectifies this defect. These data suggest that Shp1 signalling is required for the establishment of a life-long protective humoral immunity.

Suggested Citation

  • Yan-Feng Li & Shengli Xu & Xijun Ou & Kong-Peng Lam, 2014. "Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool," Nature Communications, Nature, vol. 5(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5273
    DOI: 10.1038/ncomms5273
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