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

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 ?4?1 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 ?4?1-VCAM-1 interaction rectifies this defect. These data suggest that Shp1 signalling is required for the establishment of a life-long protective humoral immunity.

SUBMITTER: Li YF 

PROVIDER: S-EPMC4083441 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature