title: The adaptor protein Sh2d3c is critical for marginal zone B cell development and function.
abstract: 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.
authors.affiliation: Lexicon Pharmaceuticals, The Woodlands, TX 77381, USA. aalshami@lexpharma.com
authors.forename: Amin
authors.initials: A
authors.lastname: Al-Shami
authors.forename: Carrie
authors.initials: C
authors.lastname: Wilkins
authors.forename: Jeannette
authors.initials: J
authors.lastname: Crisostomo
authors.forename: Dhaya
authors.initials: D
authors.lastname: Seshasayee
authors.forename: Flavius
authors.initials: F
authors.lastname: Martin
authors.forename: Nianhua
authors.initials: N
authors.lastname: Xu
authors.forename: Adisak
authors.initials: A
authors.lastname: Suwanichkul
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Anderson
authors.forename: Tamas
authors.initials: T
authors.lastname: Oravecz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D020013:Calcium Signaling / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000955:Antigens, T-Independent; C405695:Sh2d3c protein, mouse