{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:45:11Z","timestamp":1791409511048,"version":"4.3.3"},"reference-count":48,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,12,15]]},"abstract":"<jats:p>The tyrosine kinase Syk has been implicated as a key signal transducer from the B cell antigen receptor (BCR). We show here that mutation of the Syk gene completely blocks the maturation of immature B cells into recirculating cells and stops their entry into B cell follicles. Furthermore, using radiation chimeras we demonstrate that this developmental block is due to the absence of Syk in the B cells themselves. Syk-deficient B cells are shown to have the life span of normal immature B cells. If this is extended by over-expression of Bcl-2, they accumulate in the T zone and red pulp of the spleen in increased numbers, but still fail to mature to become recirculating follicular B cells. Despite this defect in maturation, Syk-deficient B cells were seen to give rise to switched as well as nonswitched splenic plasma cells. Normally only a proportion of immature B cells is recruited into the recirculating pool. Our results suggest that Syk transduces a BCR signal that is absolutely required for the positive selection of immature B cells into the recirculating B cell pool.<\/jats:p>","DOI":"10.1084\/jem.186.12.2013","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"2013-2021","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":118,"title":["Syk Tyrosine Kinase Is Required for the Positive Selection of Immature B Cells into the Recirculating B Cell Pool"],"prefix":"10.1084","volume":"186","author":[{"given":"Martin","family":"Turner","sequence":"first","affiliation":[{"name":"From the *National Institute for Medical Research, Mill Hill, London, NW7 1AA, United Kingdom; and the \u2021Department of Immunology, University of Birmingham Medical School, Birmingham, B15 2TT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Gulbranson-Judge","sequence":"additional","affiliation":[{"name":"From the *National Institute for Medical Research, Mill Hill, London, NW7 1AA, United Kingdom; and the \u2021Department of Immunology, University of Birmingham Medical School, Birmingham, B15 2TT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian E.","family":"Quinn","sequence":"additional","affiliation":[{"name":"From the *National Institute for Medical Research, Mill Hill, London, NW7 1AA, United Kingdom; and the \u2021Department of Immunology, University of Birmingham Medical School, Birmingham, B15 2TT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice E.","family":"Walters","sequence":"additional","affiliation":[{"name":"From the *National Institute for Medical Research, Mill Hill, London, NW7 1AA, United Kingdom; and the \u2021Department of Immunology, University of Birmingham Medical School, Birmingham, B15 2TT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C.M.","family":"MacLennan","sequence":"additional","affiliation":[{"name":"From the *National Institute for Medical Research, Mill Hill, London, NW7 1AA, United Kingdom; and the \u2021Department of Immunology, University of Birmingham Medical School, Birmingham, B15 2TT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor L.J.","family":"Tybulewicz","sequence":"additional","affiliation":[{"name":"From the *National Institute for Medical Research, Mill Hill, London, NW7 1AA, United Kingdom; and the \u2021Department of Immunology, University of Birmingham Medical School, Birmingham, B15 2TT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1997,12,15]]},"reference":[{"key":"2023072507244417700_B1","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/381751a0","article-title":"Clonal selection and learning in the antibody system","volume":"381","author":"Rajewsky","year":"1996","journal-title":"Nature"},{"key":"2023072507244417700_B2","first-page":"79","article-title":"B-cell production and differentiation in adult rats","volume":"54","author":"Bazin","year":"1985","journal-title":"Immunology"},{"key":"2023072507244417700_B3","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1002\/eji.1830170914","article-title":"Newly produced virgin B-cells migrate to secondary lymphoid organs but their capacity to enter follicles is restricted","volume":"17","author":"Lortan","year":"1987","journal-title":"Eur J Immunol"},{"key":"2023072507244417700_B4","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/eji.1830230209","article-title":"Only a small proportion of splenic B cells in adults are short-lived virgin cells","volume":"23","author":"Chan","year":"1993","journal-title":"Eur J Immunol"},{"key":"2023072507244417700_B5","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1084\/jem.167.3.805","article-title":"Population kinetics of rat peripheral B cells","volume":"167","author":"Gray","year":"1988","journal-title":"J Exp Med"},{"key":"2023072507244417700_B6","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1084\/jem.135.2.200","article-title":"Identification of marrow-derived and thymus-derived small lymphocytes in the lymphoid tissue and thoracic duct lymph of normal rats","volume":"135","author":"Howard","year":"1972","journal-title":"J Exp Med"},{"key":"2023072507244417700_B7","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/0008-8749(76)90191-X","article-title":"Comparative migration of B- and T-lymphocytes in the rat spleen and lymph nodes","volume":"23","author":"Nieuwenhuis","year":"1976","journal-title":"Cell Immunol"},{"key":"2023072507244417700_B8","doi-asserted-by":"crossref","first-page":"4781","DOI":"10.1073\/pnas.87.12.4781","article-title":"The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow","volume":"87","author":"F\u00f6rster","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507244417700_B9","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1084\/jem.171.3.843","article-title":"Biased expression of JH-proximal VHgenes occurs in the newly generated repertoire of neonatal and adult mice","volume":"171","author":"Malynn","year":"1990","journal-title":"J Exp Med"},{"key":"2023072507244417700_B10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/intimm\/2.1.15","article-title":"Selection of VHgene repertoires: differentiating B cells of adult bone marrow mimic fetal development","volume":"2","author":"Freitas","year":"1990","journal-title":"Int Immunol"},{"key":"2023072507244417700_B11","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1084\/jem.173.6.1357","article-title":"Most peripheral B cells in mice are ligand selected","volume":"173","author":"Gu","year":"1991","journal-title":"J Exp Med"},{"key":"2023072507244417700_B12","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1084\/jem.177.2.329","article-title":"Restricted immunoglobulin junctional diversity in neonatal B cells results from developmental selection rather than homology-based V(D)J joining","volume":"177","author":"Pandey","year":"1993","journal-title":"J Exp Med"},{"key":"2023072507244417700_B13","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1002\/j.1460-2075.1993.tb05830.x","article-title":"V-region directed selection in differentiating B lymphocytes","volume":"12","author":"Huetz","year":"1993","journal-title":"EMBO (Eur Mol Biol Organ) J"},{"key":"2023072507244417700_B14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1600-065X.1997.tb00961.x","article-title":"Signaling thresholds and interclonal competition in preimmune B-cell selection","volume":"156","author":"Cyster","year":"1997","journal-title":"Immunol Rev"},{"key":"2023072507244417700_B15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/intimm\/9.1.27","article-title":"Evidence for selection of a population of multi-reactive B cells into the splenic marginal zone","volume":"9","author":"Chen","year":"1997","journal-title":"Int Immunol"},{"key":"2023072507244417700_B16","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1002\/eji.1830270505","article-title":"Does positive selection determine the B cell repertoire?","volume":"27","author":"Hachemi-Rachedi","year":"1997","journal-title":"Eur J Immunol"},{"key":"2023072507244417700_B17","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0952-7915(97)80075-1","article-title":"Molecular mechanisms in B cell antigen receptor signalling","volume":"9","author":"Kurosaki","year":"1997","journal-title":"Curr Opin Immunol"},{"key":"2023072507244417700_B18","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/0960-9822(93)90062-S","article-title":"B-cell antigen receptor motifs have redundant signalling capabilities and bind the tyrosine kinases PTK72, Lyn and Fyn","volume":"3","author":"Law","year":"1993","journal-title":"Curr Biol"},{"key":"2023072507244417700_B19","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/j.1432-1033.1993.tb17781.x","article-title":"Association with B-cell-antigen receptor with protein-tyrosine kinase p72syk and activation by engagement of membrane IgM","volume":"213","author":"Yamada","year":"1993","journal-title":"Eur J Biochem"},{"key":"2023072507244417700_B20","doi-asserted-by":"crossref","first-page":"9524","DOI":"10.1073\/pnas.91.20.9524","article-title":"Temporal differences in the activation of three classes of non-transmembrane protein tyrosine kinases following B-cell antigen receptor surface engagement","volume":"91","author":"Saouaf","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507244417700_B21","doi-asserted-by":"crossref","first-page":"28136","DOI":"10.1016\/S0021-9258(18)46905-0","article-title":"Interactions of Lyn with the antigen receptor during B cell activation","volume":"269","author":"Burg","year":"1994","journal-title":"J Biol Chem"},{"key":"2023072507244417700_B22","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1002\/j.1460-2075.1994.tb06387.x","article-title":"Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+mobilization through distinct pathways","volume":"13","author":"Takata","year":"1994","journal-title":"EMBO (Eur Mol Biol Organ) J"},{"key":"2023072507244417700_B23","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/378298a0","article-title":"Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk","volume":"378","author":"Turner","year":"1995","journal-title":"Nature"},{"key":"2023072507244417700_B24","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/378303a0","article-title":"Syk tyrosine kinase required for mouse viability and B-cell development","volume":"378","author":"Cheng","year":"1995","journal-title":"Nature"},{"key":"2023072507244417700_B25","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1002\/eji.1830260825","article-title":"Sequential antigen-specific growth of T cells in the T zones and follicles in response to pigeon cytochrome c","volume":"26","author":"Gulbranson-Judge","year":"1996","journal-title":"Eur J Immunol"},{"key":"2023072507244417700_B26","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1084\/jem.174.3.717","article-title":"Mature murine B and T cells transferred into SCID mice can survive indefinitely and many maintain a virgin phenotype","volume":"174","author":"Sprent","year":"1991","journal-title":"J Exp Med"},{"key":"2023072507244417700_B27","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.4049\/jimmunol.149.8.2533","article-title":"Peripheral B cell maturation. I. Immature peripheral B cells in adults are heat-stable antigenhiand exhibit unique signaling characteristics","volume":"149","author":"Allman","year":"1992","journal-title":"J Immunol"},{"key":"2023072507244417700_B28","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/0092-8674(89)90761-7","article-title":"Primary antibody-forming cells and secondary B cells are generated from separate precursor cell subpopulations","volume":"59","author":"Linton","year":"1989","journal-title":"Cell"},{"key":"2023072507244417700_B29","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/354308a0","article-title":"Peripheral deletion of self-reactive B cells","volume":"354","author":"Russell","year":"1991","journal-title":"Nature"},{"key":"2023072507244417700_B30","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1084\/jem.173.5.1213","article-title":"Resolution and characterization of pro-B and pre\u2013pro-B cell stages in normal mouse bone marrow","volume":"173","author":"Hardy","year":"1991","journal-title":"J Exp Med"},{"key":"2023072507244417700_B31","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1084\/jem.178.3.951","article-title":"The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver","volume":"178","author":"Li","year":"1993","journal-title":"J Exp Med"},{"key":"2023072507244417700_B32","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1002\/j.1460-2075.1994.tb06307.x","article-title":"Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes","volume":"13","author":"Merino","year":"1994","journal-title":"EMBO (Eur Mol Biol Organ) J"},{"key":"2023072507244417700_B33","first-page":"175","article-title":"Abnormalities of the immune system induced by dysregulated bcl-2expression in transgenic mice","volume":"166","author":"Strasser","year":"1990","journal-title":"Curr Top Microbiol Immunol"},{"key":"2023072507244417700_B34","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1084\/jem.181.6.2129","article-title":"Transitional B cells are the target of negative selection in the B cell compartment","volume":"181","author":"Carsetti","year":"1995","journal-title":"J Exp Med"},{"key":"2023072507244417700_B35","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/0008-8749(74)90233-0","article-title":"Differentiation of lymphocytes in mouse bone marrow. II. Kinetics of maturation and renewal of antiglobulin-binding cells studied by double labeling","volume":"13","author":"Osmond","year":"1974","journal-title":"Cell Immunol"},{"key":"2023072507244417700_B36","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.4049\/jimmunol.151.9.4431","article-title":"Peripheral B cell maturation. II. Heat-stable antigenhisplenic B cells are an immature developmental intermediate in the production of long-lived marrow-derived B cells","volume":"151","author":"Allman","year":"1993","journal-title":"J Immunol"},{"key":"2023072507244417700_B37","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1126\/science.272.5269.1804","article-title":"Aberrant B cell development and immune response in mice with a compromised BCR complex","volume":"272","author":"Torres","year":"1996","journal-title":"Science"},{"key":"2023072507244417700_B38","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/306270a0","article-title":"Demonstration of B-cell maturation in X-linked immunodeficient mice by simultaneous three-colour immunofluorescence","volume":"306","author":"Hardy","year":"1983","journal-title":"Nature"},{"key":"2023072507244417700_B39"},{"key":"2023072507244417700_B40","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1084\/jem.165.4.949","article-title":"Development of B lymphocytes in mice heterozygous for the X-linked immunodeficiency (xid) mutation","volume":"165","author":"Forrester","year":"1987","journal-title":"J Exp Med"},{"key":"2023072507244417700_B41","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0092-8674(93)90302-7","article-title":"Normal B lymphocyte development but impaired T cell maturation in CD45-exon6 protein tyrosine phosphatase\u2013deficient mice","volume":"74","author":"Kishihara","year":"1993","journal-title":"Cell"},{"key":"2023072507244417700_B42","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1084\/jem.183.1.329","article-title":"Immunoglobulin-mediated signal transduction in B cells from CD45-deficient mice","volume":"183","author":"Benatar","year":"1996","journal-title":"J Exp Med"},{"key":"2023072507244417700_B43","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1084\/jem.183.4.1707","article-title":"CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+thymocytes, and in B cell maturation","volume":"183","author":"Byth","year":"1996","journal-title":"J Exp Med"},{"key":"2023072507244417700_B44","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/381325a0","article-title":"Regulation of B-lymphocyte negative and positive selection by tyrosine phosphatase CD45","volume":"381","author":"Cyster","year":"1996","journal-title":"Nature"},{"key":"2023072507244417700_B45","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/371389a0","article-title":"Competition for follicular niches excludes self-reactive cells from the recirculating B-cell repertoire","volume":"371","author":"Cyster","year":"1994","journal-title":"Nature"},{"key":"2023072507244417700_B46","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1084\/jem.183.5.2303","article-title":"Immunoglobulin switch transcript production in vivo related to the site and time of antigen-specific B cell activation","volume":"183","author":"Toellner","year":"1996","journal-title":"J Exp Med"},{"key":"2023072507244417700_B47","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1084\/jem.186.5.631","article-title":"Outer periarteriolar lymphoid sheath arrest and subsequent differentiation of both naive and tolerant immunoglobulin transgenic B cells is determined by B cell receptor occupancy","volume":"186","author":"Cook","year":"1997","journal-title":"J Exp Med"},{"key":"2023072507244417700_B48","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/S0092-8674(00)81798-5","article-title":"A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen","volume":"87","author":"F\u00f6rster","year":"1996","journal-title":"Cell"}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/186\/12\/2013\/1684033\/97-1758.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/186\/12\/2013\/1684033\/97-1758.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T08:02:35Z","timestamp":1690272155000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/186\/12\/2013\/7225\/Syk-Tyrosine-Kinase-Is-Required-for-the-Positive"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,12,15]]},"references-count":48,"journal-issue":{"issue":"12","published-print":{"date-parts":[[1997,12,15]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.186.12.2013","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,12,15]]}}}