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

Page view(s)
16
Checked on Mar 15, 2024
Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool
Title:
Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool
Journal Title:
Nature Communications
Keywords:
Publication Date:
30 June 2014
Citation:
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.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
Description:
ISSN:
2041-1723
Files uploaded: