The Adaptor Protein Sh2d3c Is Critical for Marginal Zone B Cell Development and Function
Autor: | Adisak Suwanichkul, Nianhua Xu, Jeannette Crisostomo, Amin Al-Shami, Stephen J. Anderson, Flavius Martin, Carrie Wilkins, Tamas Oravecz, Dhaya Seshasayee |
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Rok vydání: | 2010 |
Předmět: |
Male
medicine.medical_treatment T cell Molecular Sequence Data Immunology B-Lymphocyte Subsets Thymus Gland Biology Mice Immune system Antigen T-Lymphocyte Subsets Lymphopenia Marginal zone B-cell medicine Animals Immunology and Allergy Calcium Signaling B cell Adaptor Proteins Signal Transducing Mice Knockout Cell Differentiation Marginal zone Antigens T-Independent Cell biology Chemotaxis Leukocyte medicine.anatomical_structure Cytokine Mutagenesis Site-Directed Female Spleen Ex vivo Signal Transduction |
Zdroj: | The Journal of Immunology. 185:327-334 |
ISSN: | 1550-6606 0022-1767 |
Popis: | Sh2d3c is an adaptor protein that has been implicated in T cell activation and shown to associate with different components of the integrin signaling pathway ex vivo. However, the in vivo significance of Sh2d3c expression in the regulation of the immune response and/or hematopoietic cell lineage development is not known. In this study, we show that expression of Sh2d3c is more critical for development and function of marginal zone B (MZB) cells than for T cell maturation. Mice deficient in Sh2d3c expression (Sh2d3c−/−) had a reduced number of MZB cells, and the residual MZB cells failed to properly capture polysaccharide Ags. Activation-induced proliferation, cytokine production, and migration of Sh2d3c−/− splenic B cells were also significantly reduced in vitro compared with wild-type (Sh2d3c+/+) cells. In contrast, T cell development and function were largely normal in Sh2d3c−/− mice. The thymi of Sh2d3c−/− mice showed no maturational abnormalities, the number of splenic T cells was only modestly reduced, and the T cells responded normally to in vitro polyclonal activation. The observed B cell deficiency in the Sh2d3c−/− mice led to diminished humoral immune response against thymus-independent type 2, but not thymus-dependent Ags, which highlights the primary in vivo role of Sh2d3c in regulating B cell development and function. |
Databáze: | OpenAIRE |
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