{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:31:05Z","timestamp":1791027065634,"version":"4.1.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,1,27]]},"abstract":"<jats:p>\n                    Acquired immunity depends on proliferation and differentiation of antigen (Ag)-specific B cells in germinal centers (GCs) of lymphoid follicles in response to T cell-dependent Ags. Here, we studied the function of GC-associated nuclear protein that is selectively up-regulated in GC-B cells. B cell-specific\n                    <jats:italic>ganp<\/jats:italic>\n                    -deficient mice were compromised in affinity maturation of hapten-specific antibodies against T cell-dependent Ags with retarded development of GCs. B cell numbers and development, serum Ig levels, mitogen-induced B cell proliferation\n                    <jats:italic>in vitro<\/jats:italic>\n                    , and responses to T cell-independent Ag were nearly normal; however, the mutant B cells showed a decrease in anti-CD40-induced proliferation and an increased susceptibility to B cell apoptosis\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . B cell-specific\n                    <jats:italic>ganp<\/jats:italic>\n                    -deficient mice showed a decreased frequency of variable-region somatic mutations, especially of the high-affinity type (W\n                    <jats:sup>33<\/jats:sup>\n                    \u2192 L) in the V\n                    <jats:sub>H<\/jats:sub>\n                    186.2 region against nitrophenyl-chicken gamma globulin, whereas the class switching was normal. We conclude that GC-associated nuclear protein is necessary for generation or maintenance of B cells with high-affinity B cell Ag receptors during the maturation in GCs.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0307609100","type":"journal-article","created":{"date-parts":[[2004,1,27]],"date-time":"2004-01-27T13:23:16Z","timestamp":1075209796000},"page":"1010-1015","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["Germinal center-associated nuclear protein contributes to affinity maturation of B cell antigen receptor in T cell-dependent responses"],"prefix":"10.1073","volume":"101","author":[{"given":"Kazuhiko","family":"Kuwahara","sequence":"first","affiliation":[{"name":"Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto 860-8556, Japan; Department of Immunology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Honjo, Kumamoto 860-0811, Japan; Laboratory for Vertebrate Body Plan, RIKEN Center for Developmental Biology, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Fujimura","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto 860-8556, Japan; Department of Immunology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Honjo, Kumamoto 860-0811, Japan; Laboratory for Vertebrate Body Plan, RIKEN Center for Developmental Biology, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimasa","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto 860-8556, Japan; Department of Immunology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Honjo, Kumamoto 860-0811, Japan; Laboratory for Vertebrate Body Plan, RIKEN Center for Developmental Biology, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Nakagata","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto 860-8556, Japan; Department of Immunology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Honjo, Kumamoto 860-0811, Japan; Laboratory for Vertebrate Body Plan, RIKEN Center for Developmental Biology, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshitada","family":"Takemori","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto 860-8556, Japan; Department of Immunology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Honjo, Kumamoto 860-0811, Japan; Laboratory for Vertebrate Body Plan, RIKEN Center for Developmental Biology, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Aizawa","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto 860-8556, Japan; Department of Immunology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Honjo, Kumamoto 860-0811, Japan; Laboratory for Vertebrate Body Plan, RIKEN Center for Developmental Biology, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuo","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto 860-8556, Japan; Department of Immunology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Honjo, Kumamoto 860-0811, Japan; Laboratory for Vertebrate Body Plan, RIKEN Center for Developmental Biology, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,1,8]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/302575a0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(92)90043-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.10.040192.002043"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/381751a0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80675-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb00964.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.4.2228"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni826"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00078-7"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00079-9"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.090501.112049"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00981"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)01247-2"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/88732"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/88740"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00142-X"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141222198"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01117"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.1.2"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"4576","DOI":"10.4049\/jimmunol.156.12.4576","volume":"156","year":"1996","unstructured":"Ferguson, S. E., Han, S., Kelsoe, G. & Thompson, C. B. (1996) J. Immunol. 156, 4576\u20134581.8648099","journal-title":"J. Immunol."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1948049"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.10.1895"},{"key":"e_1_3_2_23_2","first-page":"465","volume":"7","year":"2002","unstructured":"Mackay, F. & Browning, J. (2002) Nat. Rev. Immunol. 7, 465\u2013475.","journal-title":"Nat. Rev. Immunol."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb00965.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.001001"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb00963.x"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb00957.x"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.7.2321"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00336-X"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181335698"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.39.24508"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kve026"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1993.1458"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.6.1317"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0025com"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2478(95)00006-Q"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1998.00346.x"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.3.831"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830150517"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxf065"},{"key":"e_1_3_2_41_2","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.4049\/jimmunol.152.7.3294","volume":"152","year":"1994","unstructured":"Kamesaki, H., Zwiebel, J. A., Reed, J. C. & Cossman, J. (1994) J. Immunol. 152, 3294\u20133305.8144916","journal-title":"J. Immunol."},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.4.1359.bloodjournal8841359"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.1.327"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.4.1293"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90073-6"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90095-7"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.3109\/08830189709068171"},{"key":"e_1_3_2_48_2","doi-asserted-by":"crossref","unstructured":"Smith K. G. Weiss U. Rajewsky K. Nossal G. J. & Tarlinton D. M. Immunity 1 803\u2013813.7895168","DOI":"10.1016\/S1074-7613(94)80022-7"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00100-5"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(02)86006-7"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0307609100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T16:05:54Z","timestamp":1682611554000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0307609100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,1,8]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,1,27]]}},"alternative-id":["10.1073\/pnas.0307609100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0307609100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,1,8]]},"assertion":[{"value":"2003-08-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-01-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}