{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T05:13:12Z","timestamp":1793855592302,"version":"4.6.1"},"reference-count":48,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,10,15]]},"abstract":"<jats:p>To study homeostasis of peripheral B lymphocytes in the absence of B cell influx from the bone marrow, we generated a mouse mutant in which the recombination-activating gene (RAG)-2 can be inducibly deleted. When RAG-2 was deleted at the age of 8\u201310 wk, splenic naive follicular B cells were gradually lost over a year of observation, with a half-life of \u223c4.5 mo. By contrast, the pool of marginal zone B cells in the spleen and of B-1 cells in the peritoneal cavity were kept at normal level. In lymph nodes, \u223c90% of the B cells were lost within 4 mo, and B cell numbers remained constant thereafter. Mice in which RAG-2 was deleted at birth maintained a small population of activated B cells with an increased proportion of marginal zone B cells. Additionally, an increase of the pool of IgM secreting cells and B-1a cells was observed.<\/jats:p>","DOI":"10.1084\/jem.194.8.1151","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1151-1164","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":295,"title":["Homeostasis of Peripheral B Cells in the Absence of B Cell Influx from the Bone Marrow"],"prefix":"10.1084","volume":"194","author":[{"given":"Zhenyue","family":"Hao","sequence":"first","affiliation":[{"name":"aDepartment of Immunology, Institute for Genetics, University of Cologne, D-50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Rajewsky","sequence":"additional","affiliation":[{"name":"aDepartment of Immunology, Institute for Genetics, University of Cologne, D-50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2001,10,15]]},"reference":[{"key":"2023072511191724300_R1","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":"2023072511191724300_R2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/978-1-4684-9066-4_12","article-title":"The origin of marginal-zone cells","volume":"149","author":"Kumararatne","year":"1982","journal-title":"Adv. Exp. Med. Biol."},{"key":"2023072511191724300_R3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0074-7696(08)62453-5","article-title":"Cells in the marginal zone of the spleen","volume":"132","author":"Kraal","year":"1992","journal-title":"Int. Rev. Cytol."},{"key":"2023072511191724300_R4","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1002\/eji.1830270935","article-title":"Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responses","volume":"27","author":"Oliver","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"2023072511191724300_R5","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1146\/annurev.iy.11.040193.002441","article-title":"Origin of murine B cell lineages","volume":"11","author":"Kantor","year":"1993","journal-title":"Annu. Rev. Immunol."},{"key":"2023072511191724300_R6","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":"2023072511191724300_R7","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/j.1600-065X.2000.imr017515.x","article-title":"B-cell subsets and the mature preimmune repertoire. Marginal zone and B1 B cells as part of a \u201cnatural immune memory","volume":"175","author":"Martin","year":"2000","journal-title":"Immunol. Rev."},{"key":"2023072511191724300_R8","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":"2023072511191724300_R9","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1084\/jem.185.6.1035","article-title":"Signal transducer and activator of transcription-3 (STAT3) is constitutively activated in normal, self-renewing B-1 cells but only inducibly expressed in conventional B lymphocytes","volume":"185","author":"Karras","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072511191724300_R10","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1084\/jem.189.11.1685","article-title":"Early induction of cyclin D2 expression in phorbol ester-responsive B-1 lymphocytes","volume":"189","author":"Tanguay","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072511191724300_R11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1600-065X.1986.tb01504.x","article-title":"Population dynamics of bone marrow B lymphocytes","volume":"93","author":"Osmond","year":"1986","journal-title":"Immunol. Rev."},{"key":"2023072511191724300_R12","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.4049\/jimmunol.151.9.4431","article-title":"Peripheral B cell maturation. II. Heat-stable antigen(hi) splenic 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":"2023072511191724300_R13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1600-065X.1986.tb01482.x","article-title":"Lymphocyte population kinetics in the mouse","volume":"91","author":"Freitas","year":"1986","journal-title":"Immunol. Rev."},{"key":"2023072511191724300_R14","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 antigenhi and exhibit unique signaling characteristics","volume":"149","author":"Allman","year":"1992","journal-title":"J. Immunol."},{"key":"2023072511191724300_R15","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1084\/jem.154.3.994","article-title":"Very rapid decay of mature B lymphocytes in the spleen","volume":"154","author":"de Freitas","year":"1981","journal-title":"J. Exp. Med."},{"key":"2023072511191724300_R16","doi-asserted-by":"crossref","first-page":"54","DOI":"10.4049\/jimmunol.128.1.54","article-title":"Population dynamics of B lymphocytes and their precursorsdemonstration of high turnover in the central and peripheral lymphoid organs","volume":"128","author":"Freitas","year":"1982","journal-title":"J. Immunol."},{"key":"2023072511191724300_R17","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1073\/pnas.86.8.2698","article-title":"Thymidine kinase obliterationcreation of transgenic mice with controlled immune deficiency","volume":"86","author":"Heyman","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511191724300_R18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0008-8749(76)90133-7","article-title":"B lymphocyte differentiation in lethally irradiated and reconstituted mice. I. The effect of Strontium-89 induced bone marrow aplasia on the recovery of the B cell compartment in the spleen","volume":"24","author":"Rozing","year":"1976","journal-title":"Cell. Immunol."},{"key":"2023072511191724300_R19","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1084\/jem.178.1.257","article-title":"Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody","volume":"178","author":"Grabstein","year":"1993","journal-title":"J. Exp. Med."},{"key":"2023072511191724300_R20","doi-asserted-by":"crossref","first-page":"9125","DOI":"10.1073\/pnas.90.19.9125","article-title":"Expression and function of the interleukin 7 receptor in murine lymphocytes","volume":"90","author":"Sudo","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511191724300_R21","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/eji.1830020420","article-title":"Thoracic duct lymphocytes from nude micemigratory properties and life-span","volume":"2","author":"Sprent","year":"1972","journal-title":"Eur. J. Immunol."},{"key":"2023072511191724300_R22","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/0008-8749(73)90181-0","article-title":"Circulating T and B lymphocytes of the mouse. II. Lifespan","volume":"7","author":"Sprent","year":"1973","journal-title":"Cell. Immunol."},{"key":"2023072511191724300_R23","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/0008-8749(75)90166-5","article-title":"Long-lived T and B lymphocytes in the bone marrow and thoracic duct lymph of the mouse","volume":"15","author":"Ropke","year":"1975","journal-title":"Cell. Immunol."},{"key":"2023072511191724300_R24","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":"Forster","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511191724300_R25","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1002\/eji.1830210732","article-title":"Generation of long-lived B cells in germ-free mice","volume":"21","author":"Forster","year":"1991","journal-title":"Eur. J. Immunol."},{"key":"2023072511191724300_R26","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1002\/eji.1830270521","article-title":"Influences on the lifespan of B cell subpopulations defined by different phenotypes","volume":"27","author":"Fulcher","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"2023072511191724300_R27","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/302575a0","article-title":"Somatic generation of antibody diversity","volume":"302","author":"Tonegawa","year":"1983","journal-title":"Nature."},{"key":"2023072511191724300_R28","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1126\/science.2360047","article-title":"RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination","volume":"248","author":"Oettinger","year":"1990","journal-title":"Science."},{"key":"2023072511191724300_R29","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/0092-8674(92)90030-G","article-title":"RAG-1-deficient mice have no mature B and T lymphocytes","volume":"68","author":"Mombaerts","year":"1992","journal-title":"Cell."},{"key":"2023072511191724300_R30","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/0092-8674(92)90029-C","article-title":"RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement","volume":"68","author":"Shinkai","year":"1992","journal-title":"Cell."},{"key":"2023072511191724300_R31","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1172\/JCI118828","article-title":"Conditional gene targeting","volume":"98","author":"Rajewsky","year":"1996","journal-title":"J. Clin. Invest."},{"key":"2023072511191724300_R32","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780199636778.001.0001","volume-title":"Laboratory Protocols for Conditional Gene Targeting","author":"Torres","year":"1997"},{"key":"2023072511191724300_R33","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1093\/intimm\/5.8.957","article-title":"Targeted disruption of the MHC class II Aa gene in C57BL\/6 mice","volume":"5","author":"Kontgen","year":"1993","journal-title":"Int. Immunol."},{"key":"2023072511191724300_R34","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1126\/science.7660125","article-title":"Inducible gene targeting in mice","volume":"269","author":"Kuhn","year":"1995","journal-title":"Science."},{"key":"2023072511191724300_R35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1084\/jem.177.1.45","article-title":"Immunoglobulin D (IgD)-deficient mice reveal an auxiliary receptor function for IgD in antigen-mediated recruitment of B cells","volume":"177","author":"Roes","year":"1993","journal-title":"J. Exp. Med."},{"key":"2023072511191724300_R36","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0022-1759(83)90308-3","article-title":"A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells","volume":"65","author":"Czerkinsky","year":"1983","journal-title":"J. Immunol. Methods."},{"key":"2023072511191724300_R37","doi-asserted-by":"crossref","first-page":"5080","DOI":"10.1093\/nar\/23.24.5080","article-title":"A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells","volume":"23","author":"Schwenk","year":"1995","journal-title":"Nucleic Acids Res."},{"key":"2023072511191724300_R38","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.4049\/jimmunol.159.3.1557","article-title":"Mouse complement receptors type 1 (CR1;CD35) and type 2 (CR2;CD21)expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL\/lpr mice","volume":"159","author":"Takahashi","year":"1997","journal-title":"J. Immunol."},{"key":"2023072511191724300_R39","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1600-065X.2000.imr017520.x","article-title":"B-1 cellsthe lineage question revisited","volume":"175","author":"Herzenberg","year":"2000","journal-title":"Immunol. Rev."},{"key":"2023072511191724300_R40","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/icb.1997.69","article-title":"B cell life spana review","volume":"75","author":"Fulcher","year":"1997","journal-title":"Immunol. Cell Biol."},{"key":"2023072511191724300_R41","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1084\/jem.174.3.717","article-title":"Mature murine B and T cells transferred to SCID mice can survive indefinitely and many maintain a virgin phenotype","volume":"174","author":"Sprent","year":"1991","journal-title":"J. Exp. Med"},{"key":"2023072511191724300_R42","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1084\/jem.189.2.319","article-title":"Transfer of small resting B cells into immunodeficient hosts results in the selection of a self-renewing activated B cell population","volume":"189","author":"Agenes","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072511191724300_R43","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S0952-7915(00)00098-4","article-title":"Development and function of B-1 cells","volume":"12","author":"Hayakawa","year":"2000","journal-title":"Curr. Opin. Immunol."},{"key":"2023072511191724300_R44","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/0952-7915(95)80053-0","article-title":"Natural autoantibodies","volume":"7","author":"Coutinho","year":"1995","journal-title":"Curr. Opin. Immunol."},{"key":"2023072511191724300_R45","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1084\/jem.194.8.1141","article-title":"Arrested B lymphopoesis and persistence of activated B cells in adult interleukin 7\u2212\/\u2212 mice","volume":"194","author":"Carvalho","year":"2001","journal-title":"J. Exp. Med."},{"key":"2023072511191724300_R46","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/intimm\/1.1.75","article-title":"Many of the IgA producing plasma cells in murine gut are derived from self-replenishing precursors in the peritoneal cavity","volume":"1","author":"Kroese","year":"1989","journal-title":"Int. Immunol."},{"key":"2023072511191724300_R47","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/0092-8674(89)90748-4","article-title":"Toward a layered immune system","volume":"59","author":"Herzenberg","year":"1989","journal-title":"Cell."},{"key":"2023072511191724300_R48","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1126\/science.285.5424.113","article-title":"Positive selection of natural autoreactive B cells","volume":"285","author":"Hayakawa","year":"1999","journal-title":"Science."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/194\/8\/1151\/1704448\/011005.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/194\/8\/1151\/1704448\/011005.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T17:21:18Z","timestamp":1704388878000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/194\/8\/1151\/98\/Homeostasis-of-Peripheral-B-Cells-in-the-Absence"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,10,15]]},"references-count":48,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2001,10,15]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.194.8.1151","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,10,15]]}}}