{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:10:35Z","timestamp":1790687435696,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:00:00Z","timestamp":1506988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1054925"],"award-info":[{"award-number":["1054925"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p>\n                    Bcl6 (B\u2010cell lymphoma 6) is a transcriptional repressor and critical mediator of the germinal center reaction during a T\u2010cell\u2010dependent antibody response, where it enables somatic hypermutation of immunoglobulin genes and inhibits terminal differentiation via repression of Blimp1. It can also contribute to the development of diffuse large B\u2010cell lymphoma when expressed inappropriately. Bcl6 regulation is mediated both at the transcriptional and post\u2010transcriptional levels, and in particular a strong signal through the B\u2010cell receptor causes rapid proteasomal degradation of Bcl6. Despite the importance of Bcl6 in both immunity and cancer, little is known about how other extrinsic factors regulate Bcl6 in B cells. Here we show that Bcl6 is indeed highly unstable in B cells after a B\u2010cell receptor (BCR) signal, but that the T\u2010cell\u2010derived cytokines interleukin 4 (IL4) and IL21 counteract BCR\u2010mediated degradation, preserving Bcl6 protein levels. Stat6, downstream of IL4, can induce Bcl6 transcription directly.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , B\u2010cell intrinsic loss of IL4 or IL21 signaling reduces the magnitude or duration of the GC response, respectively, while their combined loss almost completely eliminates the GC response. This work provides key insights into the effect mediated by T\u2010follicular helper cytokines on Bcl6 regulation.\n                  <\/jats:p>","DOI":"10.1038\/icb.2017.71","type":"journal-article","created":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T09:21:11Z","timestamp":1504689671000},"page":"925-932","source":"Crossref","is-referenced-by-count":62,"title":["IL4 and IL21 cooperate to induce the high Bcl6 protein level required for germinal center formation"],"prefix":"10.1111","volume":"95","author":[{"given":"St\u00e9phane","family":"Chevrier","sequence":"first","affiliation":[{"name":"Molecular Immunology Division, The Walter and Eliza Hall Institute  Parkville Victoria Australia"},{"name":"Department of Medical Biology, The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Kratina","sequence":"additional","affiliation":[{"name":"Molecular Immunology Division, The Walter and Eliza Hall Institute  Parkville Victoria Australia"},{"name":"Department of Medical Biology, The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Emslie","sequence":"additional","affiliation":[{"name":"Molecular Immunology Division, The Walter and Eliza Hall Institute  Parkville Victoria Australia"},{"name":"Department of Medical Biology, The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Tarlinton","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, The University of Melbourne  Parkville Victoria Australia"},{"name":"Immunology Division, The Walter and Eliza Hall Institute of Medical Research  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn M","family":"Corcoran","sequence":"additional","affiliation":[{"name":"Molecular Immunology Division, The Walter and Eliza Hall Institute  Parkville Victoria Australia"},{"name":"Department of Medical Biology, The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,3]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2012.01112.x"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.03.037"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.12.5257.bloodjournal87125257"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.13.1953"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac4919"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.11.001"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.12.008"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-054973"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042325"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1997"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2059"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018552"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.12.018"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1077002"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344203"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091777"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091738"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111504"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3050"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01620-12"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxl041"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.232581199"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2006.01.004"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501463"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2013.05.003"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3554"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/antib5010005"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3154"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/380627a0"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3293"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131831"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5312.589"}],"container-title":["Immunology 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