{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:11:22Z","timestamp":1770718282735,"version":"3.49.0"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5097","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1993,2,12]]},"abstract":"<jats:p>\n            Upon activation, B lymphocytes can change the class of the antibody they express by immunoglobulin class switch recombination. Cytokines can direct this recombination to distinct classes by the specific activation of repetitive recombinogenic DNA sequences, the switch regions. Recombination to a particular switch region (s\n            <jats:sub>\u03b3<\/jats:sub>\n            1) was abolished in mice that were altered to lack sequences that are 5\u2032 to the s\n            <jats:sub>\u03b3<\/jats:sub>\n            1 region. This result directly implicates the functional importance of 5\u2032 switch region flanking sequences in the control of class switch recombination. Mutant mice exhibit a selective agammaglobulinemia and may be useful in the assessment of the biological importance of immunoglobulin G1.\n          <\/jats:p>","DOI":"10.1126\/science.8438159","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T23:05:09Z","timestamp":1160089509000},"page":"984-987","source":"Crossref","is-referenced-by-count":245,"title":["Shutdown of Class Switch Recombination by Deletion of a Switch Region Control Element"],"prefix":"10.1126","volume":"259","author":[{"given":"Steffen","family":"Jung","sequence":"first","affiliation":[{"name":"Institute for Genetics, University of Cologne, D-5000 Cologne 41, Germany."}]},{"given":"Klaus","family":"Rajewsky","sequence":"additional","affiliation":[{"name":"Institute for Genetics, University of Cologne, D-5000 Cologne 41, Germany."}]},{"given":"Aandreas","family":"Radbruch","sequence":"additional","affiliation":[{"name":"Institute for Genetics, University of Cologne, D-5000 Cologne 41, Germany."}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/eji.1830180716","volume":"18","year":"1988","unstructured":"BERGSTEDTLINDQV.S, INTERLEUKIN-4 INSTRUCTS UNCOMMITTED LYMPHOCYTES-B TO SWITCH TO IGG1 AND IGE, EUROPEAN JOURNAL OF IMMUNOLOGY 18: 1073 (1988).","journal-title":"EUROPEAN JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_2_1","first-page":"2829","volume":"86","year":"1989","unstructured":"BERTON, M.T., SYNTHESIS OF GERM-LINE GAMMA-1 IMMUNOGLOBULIN HEAVY-CHAIN TRANSCRIPTS IN RESTING B-CELLS - INDUCTION BY INTERLEUKIN-4 AND INHIBITION BY INTERFERON-GAMMA, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 86: 2829 (1989).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/0092-8674(80)90487-0","volume":"21","year":"1980","unstructured":"BROACH, J.R., REPLICATION AND RECOMBINATION FUNCTIONS ASSOCIATED WITH THE YEAST PLASMID, 2-MU CIRCLE, CELL 21: 501 (1980).","journal-title":"CELL"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1002\/eji.1830201018","volume":"20","year":"1990","unstructured":"BURGER, C, PROTECTIVE METHYLATION OF IMMUNOGLOBULIN AND T-CELL RECEPTOR (TCR) GENE LOCI PRIOR TO INDUCTION OF CLASS SWITCH AND TCR RECOMBINATION, EUROPEAN JOURNAL OF IMMUNOLOGY 20: 2285 (1990).","journal-title":"EUROPEAN JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1146\/annurev.iy.08.040190.003441","volume":"8","year":"1990","unstructured":"ESSER, C, IMMUNOGLOBULIN CLASS SWITCHING - MOLECULAR AND CELLULAR ANALYSIS, ANNUAL REVIEW OF IMMUNOLOGY 8: 717 (1990).","journal-title":"ANNUAL REVIEW OF IMMUNOLOGY"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/j.1460-2075.1989.tb03401.x","volume":"8","year":"1989","unstructured":"ESSER, C, RAPID INDUCTION OF TRANSCRIPTION OF UNREARRANGED S-GAMMA-1 SWITCH REGIONS IN ACTIVATED MURINE B-CELLS BY INTERLEUKIN-4, EMBO JOURNAL 8: 483 (1989).","journal-title":"EMBO JOURNAL"},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/j.1460-2075.1990.tb08087.x","volume":"9","year":"1990","unstructured":"FERRIER, P, SEPARATE ELEMENTS CONTROL DJ AND VDJ REARRANGEMENT IN A TRANSGENIC RECOMBINATION SUBSTRATE, EMBO JOURNAL 9: 117 (1990).","journal-title":"EMBO JOURNAL"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/326292a0","volume":"326","year":"1987","unstructured":"HOOPER, M, HPRT-DEFICIENT (LESCH-NYHAN) MOUSE EMBRYOS DERIVED FROM GERMLINE COLONIZATION BY CULTURED-CELLS, NATURE 326: 292 (1987).","journal-title":"NATURE"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/0161-5890(92)90063-4","volume":"29","year":"1992","unstructured":"ILLGES, H, DNA-BINDING SITES 5' OF THE IGG1 SWITCH REGION COMPRISING IL4 INDUCIBILITY AND B-CELL SPECIFICITY, MOLECULAR IMMUNOLOGY 29: 1265 (1992).","journal-title":"MOLECULAR IMMUNOLOGY"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1084\/jem.155.3.734","volume":"155","year":"1982","unstructured":"ISAKSON, P.C., T-CELL-DERIVED B-CELL DIFFERENTIATION FACTOR(S) - EFFECT ON THE ISOTYPE SWITCH OF MURINE B-CELLS, JOURNAL OF EXPERIMENTAL MEDICINE 155: 734 (1982).","journal-title":"JOURNAL OF EXPERIMENTAL MEDICINE"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/350423a0"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1948049"},{"key":"e_1_2_1_13_1","doi-asserted-by":"crossref","first-page":"952","DOI":"10.4049\/jimmunol.144.3.952","volume":"144","year":"1990","unstructured":"LEBMAN, D.A., MECHANISM FOR TRANSFORMING GROWTH FACTOR-BETA AND IL-2 ENHANCEMENT OF IGA EXPRESSION IN LIPOPOLYSACCHARIDE-STIMULATED B-CELL CULTURES, JOURNAL OF IMMUNOLOGY 144: 952 (1990).","journal-title":"JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_14_1","first-page":"4154","volume":"89","year":"1992","unstructured":"LEUNG, H, TRANSCRIPTIONAL REGULATORY ELEMENTS STIMULATE RECOMBINATION IN EXTRACHROMOSOMAL SUBSTRATES CARRYING IMMUNOGLOBULIN SWITCH-REGION SEQUENCES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89: 4154 (1992).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/336348a0","volume":"336","year":"1988","unstructured":"MANSOUR, S.L., DISRUPTION OF THE PROTO-ONCOGENE INT-2 IN MOUSE EMBRYO-DERIVED STEM-CELLS - A GENERAL STRATEGY FOR TARGETING MUTATIONS TO NON-SELECTABLE GENES, NATURE 336: 348 (1988).","journal-title":"NATURE"},{"key":"e_1_2_1_16_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.4049\/jimmunol.149.3.1075","volume":"149","year":"1992","unstructured":"MILLS, F.C., IG MU-EPSILON ISOTYPE SWITCH IN IL-4-TREATED HUMAN B-LYMPHOBLASTOID CELLS - EVIDENCE FOR A SEQUENTIAL SWITCH, JOURNAL OF IMMUNOLOGY 149: 1075 (1992).","journal-title":"JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_17_1","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.4049\/jimmunol.136.7.2674","volume":"136","year":"1986","unstructured":"MOWATT, M.R., DNA-SEQUENCE OF THE MURINE GAMMA-1 SWITCH SEGMENT REVEALS NOVEL STRUCTURAL ELEMENTS, JOURNAL OF IMMUNOLOGY 136: 2674 (1986).","journal-title":"JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/338035a0"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1900642"},{"key":"e_1_2_1_20_1","first-page":"3954","volume":"83","year":"1986","unstructured":"RADBRUCH, A, CLASS SWITCH RECOMBINATION IS IGG1 SPECIFIC ON ACTIVE AND INACTIVE IGH LOCI OF IGG1-SECRETING B-CELL BLASTS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83: 3954 (1986).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/intimm\/2.7.621","volume":"2","year":"1990","unstructured":"ROTHMAN, P, STRUCTURE AND EXPRESSION OF GERMLINE IMMUNOGLOBULIN-GAMMA-3 HEAVY-CHAIN GENE TRANSCRIPTS - IMPLICATIONS FOR MITOGEN AND LYMPHOKINE DIRECTED CLASS-SWITCHING, INTERNATIONAL IMMUNOLOGY 2: 621 (1990).","journal-title":"INTERNATIONAL IMMUNOLOGY"},{"key":"e_1_2_1_22_1","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1084\/jem.168.6.2385","volume":"168","year":"1988","unstructured":"ROTHMAN, P, MITOGEN PLUS INTERLEUKIN-4 INDUCTION OF C-EPSILON TRANSCRIPTS IN B-LYMPHOID CELLS, JOURNAL OF EXPERIMENTAL MEDICINE 168: 2385 (1988).","journal-title":"JOURNAL OF EXPERIMENTAL MEDICINE"},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1093\/intimm\/1.6.570","volume":"1","year":"1989","unstructured":"SCHMITZ, J, INT IMMUNOL 1: 570 (1989).","journal-title":"INT IMMUNOL"},{"key":"e_1_2_1_24_1","first-page":"322","volume":"11","year":"1991","unstructured":"SCHULTES, N.P., A POLY(DA-DT) TRACT IS A COMPONENT OF THE RECOMBINATION INITIATION SITE AT THE ARG4 LOCUS IN SACCHAROMYCES-CEREVISIAE, MOLECULAR AND CELLULAR BIOLOGY 11: 322 (1991).","journal-title":"MOLECULAR AND CELLULAR BIOLOGY"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.4049\/jimmunol.149.1.60","volume":"149","year":"1992","unstructured":"SCHULTZ, C.L., T-HELPER CELL-MEMBRANES PROMOTE IL-4-INDEPENDENT EXPRESSION OF GERM-LINE C-GAMMA-1 TRANSCRIPTS IN B-CELLS, JOURNAL OF IMMUNOLOGY 149: 60 (1992).","journal-title":"JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_26_1","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/eji.1830200520","volume":"20","year":"1990","unstructured":"SEVERINSON, E, INDUCTION OF GERM-LINE IMMUNOGLOBULIN HEAVY-CHAIN TRANSCRIPTS BY MITOGENS AND INTERLEUKINS PRIOR TO SWITCH RECOMBINATION, EUROPEAN JOURNAL OF IMMUNOLOGY 20: 1079 (1990).","journal-title":"EUROPEAN JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/0092-8674(82)90204-5","volume":"28","year":"1982","unstructured":"SHIMIZU, A, ORGANIZATION OF THE CONSTANT-REGION GENE FAMILY OF THE MOUSE IMMUNOGLOBULIN HEAVY-CHAIN, CELL 28: 499 (1982).","journal-title":"CELL"},{"key":"e_1_2_1_28_1","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/eji.1830220723","volume":"22","year":"1992","unstructured":"SIEBENKOTTEN, G, THE MURINE IGG1\/IGE CLASS SWITCH PROGRAM, EUROPEAN JOURNAL OF IMMUNOLOGY 22: 1827 (1992).","journal-title":"EUROPEAN JOURNAL OF IMMUNOLOGY"},{"key":"e_1_2_1_29_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/j.1460-2075.1986.tb04182.x","volume":"5","year":"1986","unstructured":"STAVNEZERNORDGR.J, SPECIFICITY OF IMMUNOGLOBULIN HEAVY-CHAIN SWITCH CORRELATES WITH ACTIVITY OF GERMLINE HEAVY-CHAIN GENES PRIOR TO SWITCHING, EMBO JOURNAL 5: 95 (1986).","journal-title":"EMBO JOURNAL"},{"key":"e_1_2_1_30_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/0092-8674(87)90646-5","volume":"51","year":"1987","unstructured":"THOMAS, K.R., SITE-DIRECTED MUTAGENESIS BY GENE TARGETING IN MOUSE EMBRYO-DERIVED STEM-CELLS, CELL 51: 503 (1987).","journal-title":"CELL"},{"key":"e_1_2_1_31_1","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/0092-8674(87)90714-8","volume":"48","year":"1987","unstructured":"VOELKELMEIMAN, K, RECOMBINATION-STIMULATING SEQUENCES IN YEAST RIBOSOMAL DNA CORRESPOND TO SEQUENCES REGULATING TRANSCRIPTION BY RNA POLYMERASE-I, CELL 48: 1071 (1987).","journal-title":"CELL"},{"key":"e_1_2_1_32_1","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/336684a0","volume":"336","year":"1988","unstructured":"Williams, R. L., Nature 336:684 (1988).","journal-title":"Nature"},{"key":"e_1_2_1_33_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1155\/1990\/47659","volume":"1","year":"1990","unstructured":"XU, M, DEV IMMUNOL 1: 11 (1990).","journal-title":"DEV IMMUNOL"},{"key":"e_1_2_1_34_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/j.1460-2075.1992.tb05037.x","volume":"11","year":"1992","unstructured":"XU, M.Z., REGULATION OF TRANSCRIPTION OF IMMUNOGLOBULIN GERM-LINE GAMMA-1 RNA - ANALYSIS OF THE PROMOTER ENHANCER, EMBO JOURNAL 11: 145 (1992).","journal-title":"EMBO JOURNAL"},{"key":"e_1_2_1_35_1","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1002\/j.1460-2075.1986.tb04637.x","volume":"5","year":"1986","unstructured":"YANCOPOULOS, G.D., SECONDARY GENOMIC REARRANGEMENT EVENTS IN PRE-B CELLS - VHDJH REPLACEMENT BY A LINE-1 SEQUENCE AND DIRECTED CLASS SWITCHING, EMBO JOURNAL 5: 3259 (1986).","journal-title":"EMBO JOURNAL"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.8438159","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T10:22:01Z","timestamp":1705314121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.8438159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,2,12]]},"references-count":35,"journal-issue":{"issue":"5097","published-print":{"date-parts":[[1993,2,12]]}},"alternative-id":["10.1126\/science.8438159"],"URL":"https:\/\/doi.org\/10.1126\/science.8438159","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,2,12]]}}}