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

Yan-Feng Li, Shengli Xu, Xijun Ou and Kong-Peng Lam ()
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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
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

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5273

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