title: 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 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.
authors: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore.
authors: Yan-Feng
authors: YF
authors: Li
authors: 1] Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore [2] Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
authors: Shengli
authors: S
authors: Xu
authors: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore.
authors: Xijun
authors: X
authors: Ou
authors: 1] Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore 138668, Singapore [2] Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore [3] Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore [4] Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
authors: Kong-Peng
authors: KP
authors: Lam
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology*; D002454:Cell Differentiation; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology; D005260:Female; D008297:Male; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase