{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:36:49Z","timestamp":1791067009357,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2010,7,1]],"date-time":"2010-07-01T00:00:00Z","timestamp":1277942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2212\/\u2212) 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\u2212\/\u2212 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\u2212\/\u2212 mice. The thymi of Sh2d3c\u2212\/\u2212 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\u2212\/\u2212 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1000096","type":"journal-article","created":{"date-parts":[[2010,5,27]],"date-time":"2010-05-27T03:19:21Z","timestamp":1274930361000},"page":"327-334","source":"Crossref","is-referenced-by-count":13,"title":["The Adaptor Protein Sh2d3c Is Critical for Marginal Zone B Cell Development and Function"],"prefix":"10.1093","volume":"185","author":[{"given":"Amin","family":"Al-Shami","sequence":"first","affiliation":[{"name":"Lexicon Pharmaceuticals , The Woodlands, TX 77381"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Wilkins","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals , The Woodlands, TX 77381"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette","family":"Crisostomo","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals , The Woodlands, TX 77381"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhaya","family":"Seshasayee","sequence":"additional","affiliation":[{"name":"Department of Immunology , Genentech, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavius","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Immunology , Genentech, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianhua","family":"Xu","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals , The Woodlands, TX 77381"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adisak","family":"Suwanichkul","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals , The Woodlands, TX 77381"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J","family":"Anderson","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals , The Woodlands, TX 77381"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamas","family":"Oravecz","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals , The Woodlands, TX 77381"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,7,1]]},"reference":[{"key":"2025032411380383800_r1","doi-asserted-by":"crossref","first-page":"31941","DOI":"10.1074\/jbc.274.45.31941","article-title":"A novel signaling intermediate, SHEP1, directly couples Eph receptors to R-Ras and Rap1A","volume":"274","author":"Dodelet","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2025032411380383800_r2","doi-asserted-by":"crossref","first-page":"6404","DOI":"10.1074\/jbc.275.9.6404","article-title":"Chat, a Cas\/HEF1-associated adaptor protein that integrates multiple signaling pathways","volume":"275","author":"Sakakibara","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2025032411380383800_r3","doi-asserted-by":"crossref","first-page":"10047","DOI":"10.1074\/jbc.274.15.10047","article-title":"NSP1 defines a novel family of adaptor proteins linking integrin and tyrosine kinase receptors to the c-Jun N-terminal kinase\/stress-activated protein kinase signaling pathway","volume":"274","author":"Lu","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2025032411380383800_r4","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1093\/emboj\/17.10.2799","article-title":"Identification of BCAR3 by a random search for genes involved in antiestrogen resistance of human breast cancer cells","volume":"17","author":"van Agthoven","year":"1998","journal-title":"EMBO J."},{"key":"2025032411380383800_r5","doi-asserted-by":"crossref","first-page":"41892","DOI":"10.1074\/jbc.M402929200","article-title":"SHEP1 function in cell migration is impaired by a single amino acid mutation that disrupts association with the scaffolding protein cas but not with Ras GTPases","volume":"279","author":"Dail","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2025032411380383800_r6","doi-asserted-by":"crossref","first-page":"6012","DOI":"10.1074\/jbc.M207942200","article-title":"A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell receptor-mediated interleukin-2 production by Jurkat cells","volume":"278","author":"Sakakibara","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2025032411380383800_r7","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.febslet.2005.11.070","article-title":"Molecular determinants for interaction of SHEP1 with Cas localize to a highly solvent-protected region in the complex","volume":"580","author":"Derunes","year":"2006","journal-title":"FEBS Lett."},{"key":"2025032411380383800_r8","first-page":"2331","article-title":"Molecular cloning of a cDNA encoding a phosphoprotein, Efs, which contains a Src homology 3 domain and associates with Fyn","volume":"11","author":"Ishino","year":"1995","journal-title":"Oncogene"},{"key":"2025032411380383800_r9","doi-asserted-by":"crossref","first-page":"3748","DOI":"10.1002\/j.1460-2075.1994.tb06684.x","article-title":"A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner","volume":"13","author":"Sakai","year":"1994","journal-title":"EMBO J."},{"key":"2025032411380383800_r10","doi-asserted-by":"crossref","first-page":"4915","DOI":"10.1242\/jcs.00207","article-title":"Novel function of Chat in controlling cell adhesion via Cas-Crk-C3G-pathway-mediated Rap1 activation","volume":"115","author":"Sakakibara","year":"2002","journal-title":"J. Cell Sci."},{"key":"2025032411380383800_r11","doi-asserted-by":"crossref","first-page":"28264","DOI":"10.1074\/jbc.M303535200","article-title":"Synergistic promotion of c-Src activation and cell migration by Cas and AND-34\/BCAR3","volume":"278","author":"Riggins","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2025032411380383800_r12","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.0105-2896.2006.00350.x","article-title":"Trafficking from the bone marrow to the thymus: a prerequisite for thymopoiesis","volume":"209","author":"Schwarz","year":"2006","journal-title":"Immunol. Rev."},{"key":"2025032411380383800_r13","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1084\/jem.194.8.1151","article-title":"Homeostasis of peripheral B cells in the absence of B cell influx from the bone marrow","volume":"194","author":"Hao","year":"2001","journal-title":"J. Exp. Med."},{"key":"2025032411380383800_r14","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1146\/annurev.immunol.23.021704.115728","article-title":"Marginal zone B cells","volume":"23","author":"Pillai","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"2025032411380383800_r15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/76859","article-title":"B cells on the front line","volume":"1","author":"Cyster","year":"2000","journal-title":"Nat. Immunol."},{"key":"2025032411380383800_r16","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.coi.2005.04.009","article-title":"Marginal zone B cells in lymphocyte activation and regulation","volume":"17","author":"Lopes-Carvalho","year":"2005","journal-title":"Curr. Opin. Immunol."},{"key":"2025032411380383800_r17","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1046\/j.1365-2249.2002.01953.x","article-title":"The dual function of the splenic marginal zone: essential for initiation of anti-TI-2 responses but also vital in the general first-line defense against blood-borne antigens","volume":"130","author":"Zandvoort","year":"2002","journal-title":"Clin. Exp. Immunol."},{"key":"2025032411380383800_r18","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nri799","article-title":"Marginal-zone B cells","volume":"2","author":"Martin","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"2025032411380383800_r19","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0952-7915(00)00204-1","article-title":"B1 cells: similarities and differences with other B cell subsets","volume":"13","author":"Martin","year":"2001","journal-title":"Curr. Opin. Immunol."},{"key":"2025032411380383800_r20","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/S1074-7613(01)00129-7","article-title":"Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens","volume":"14","author":"Martin","year":"2001","journal-title":"Immunity"},{"key":"2025032411380383800_r21","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.2144\/99266rr02","article-title":"Construction of gene targeting vectors from lambda KOS genomic libraries","volume":"26","author":"Wattler","year":"1999","journal-title":"BioTechniques"},{"key":"2025032411380383800_r22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/76882","article-title":"Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral response","volume":"1","author":"Guinamard","year":"2000","journal-title":"Nat. Immunol."},{"key":"2025032411380383800_r23","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.immuni.2007.04.012","article-title":"Ablation of ribosomal protein L22 selectively impairs alphabeta T cell development by activation of a p53-dependent checkpoint","volume":"26","author":"Anderson","year":"2007","journal-title":"Immunity"},{"key":"2025032411380383800_r24","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1084\/jem.20031975","article-title":"A role for thymic stromal lymphopoietin in CD4+ T cell development","volume":"200","author":"Al-Shami","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025032411380383800_r25","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/0470014067.ch10","volume-title":"Model Organisms in Drug Discovery.","author":"Beltrandelrio","year":"2003"},{"key":"2025032411380383800_r26","first-page":"665","article-title":"Marginal metallophilic cells of the mouse spleen identified by a monoclonal antibody","volume":"58","author":"Kraal","year":"1986","journal-title":"Immunology"},{"key":"2025032411380383800_r27","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1084\/jem.20030684","article-title":"Macrophages control the retention and trafficking of B lymphocytes in the splenic marginal zone","volume":"198","author":"Karlsson","year":"2003","journal-title":"J. Exp. Med."},{"key":"2025032411380383800_r28","doi-asserted-by":"crossref","first-page":"7198","DOI":"10.4049\/jimmunol.162.12.7198","article-title":"IgMhighCD21high lymphocytes enriched in the splenic marginal zone generate effector cells more rapidly than the bulk of follicular B cells","volume":"162","author":"Oliver","year":"1999","journal-title":"J. Immunol."},{"key":"2025032411380383800_r29","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1084\/jem.194.1.45","article-title":"A coordinated change in chemokine responsiveness guides plasma cell movements","volume":"194","author":"Hargreaves","year":"2001","journal-title":"J. Exp. Med."},{"key":"2025032411380383800_r30","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1084\/jem.184.3.1101","article-title":"A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)","volume":"184","author":"Bleul","year":"1996","journal-title":"J. Exp. Med."},{"key":"2025032411380383800_r31","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/35018581","article-title":"A chemokine-driven positive feedback loop organizes lymphoid follicles","volume":"406","author":"Ansel","year":"2000","journal-title":"Nature"},{"key":"2025032411380383800_r32","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev.immunol.23.021704.115628","article-title":"Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs","volume":"23","author":"Cyster","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"2025032411380383800_r33","doi-asserted-by":"crossref","first-page":"14301","DOI":"10.1074\/jbc.273.23.14301","article-title":"Identification of a new Pyk2 isoform implicated in chemokine and antigen receptor signaling","volume":"273","author":"Dikic","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2025032411380383800_r34","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.0105-2896.2004.0108.x","article-title":"Alternative routes to maturity: branch points and pathways for generating follicular and marginal zone B cells","volume":"197","author":"Allman","year":"2004","journal-title":"Immunol. Rev."},{"key":"2025032411380383800_r35","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S1074-7613(02)00270-4","article-title":"A point mutation in the constant region of Ig lambda1 prevents normal B cell development due to defective BCR signaling","volume":"16","author":"Sun","year":"2002","journal-title":"Immunity"},{"key":"2025032411380383800_r36","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S1074-7613(01)00135-2","article-title":"The follicular versus marginal zone B lymphocyte cell fate decision is regulated by Aiolos, Btk, and CD21","volume":"14","author":"Cariappa","year":"2001","journal-title":"Immunity"},{"key":"2025032411380383800_r37","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.1002\/(SICI)1521-4141(199910)29:10<3285::AID-IMMU3285>3.0.CO;2-P","article-title":"CD1high B cells: a population of mixed origin","volume":"29","author":"Makowska","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"2025032411380383800_r38","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S1074-7613(00)80157-0","article-title":"Positive selection from newly formed to marginal zone B cells depends on the rate of clonal production, CD19, and btk","volume":"12","author":"Martin","year":"2000","journal-title":"Immunity"},{"key":"2025032411380383800_r39","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1093\/intimm\/dxh142","article-title":"Marginal zone B cells transport and deposit IgM-containing immune complexes onto follicular dendritic cells","volume":"16","author":"Ferguson","year":"2004","journal-title":"Int. Immunol."},{"key":"2025032411380383800_r40","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.4049\/jimmunol.175.6.3492","article-title":"Crk-associated substrate lymphocyte type is required for lymphocyte trafficking and marginal zone B cell maintenance","volume":"175","author":"Seo","year":"2005","journal-title":"J. Immunol."},{"key":"2025032411380383800_r41","doi-asserted-by":"crossref","first-page":"563","DOI":"10.4049\/jimmunol.163.2.563","article-title":"Cas-L is required for beta 1 integrin-mediated costimulation in human T cells","volume":"163","author":"Kamiguchi","year":"1999","journal-title":"J. Immunol."},{"key":"2025032411380383800_r42","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1242\/jcs.111.14.1981","article-title":"Expression and characterization of splice variants of PYK2, a focal adhesion kinase-related protein","volume":"111","author":"Xiong","year":"1998","journal-title":"J. Cell Sci."},{"key":"2025032411380383800_r43","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1002\/(SICI)1521-4141(199811)28:11<3867::AID-IMMU3867>3.0.CO;2-K","article-title":"Pyk2 is differentially regulated by beta1 integrin- and CD28-mediated co-stimulation in human CD4+ T lymphocytes","volume":"28","author":"van Seventer","year":"1998","journal-title":"Eur. J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/185\/1\/327\/62473854\/1000096.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/185\/1\/327\/62473854\/1000096.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T21:19:47Z","timestamp":1743196787000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/185\/1\/327\/7977491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7,1]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,7,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1000096","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,7]]},"published":{"date-parts":[[2010,7,1]]}}}