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

Nature communications (2014-07-01)
Yan-Feng Li, Shengli Xu, Xijun Ou, Kong-Peng Lam
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 Ptpn6(f/f)Aicda(Cre/+) mice with Shp1 ablated only in activated B cells. We show that Ptpn6(f/f)Aicda(Cre/+) 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.

MATERIALS
Product Number
Brand
Product Description

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Aluminum potassium sulfate dodecahydrate, ACS reagent, ≥98%
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