0 5 BCL-6 BCL-6 NNP 6 16 expression expression NN 17 23 during during IN 24 30 B-cell b-cell NN 31 41 activation activation NN 41 42 . . . 44 58 Translocations translocation NNS 59 68 involving involve VBG 69 72 the the DT 73 78 BCL-6 bcl-6 NN 79 83 gene gene NN 84 87 are be VBP 88 94 common common JJ 95 97 in in IN 98 101 the the DT 102 109 diffuse diffuse JJ 110 115 large large JJ 116 120 cell cell NN 121 128 subtype subtype NN 129 131 of of IN 132 143 non-Hodgkin non-hodgkin JJ 143 145 ’s 's POS 146 154 lymphoma lymphoma NN 154 155 . . . 156 166 Invariably invariably RB 166 167 , , , 168 171 the the DT 172 177 BCL-6 bcl-6 NN 178 184 coding coding NN 185 191 region region NN 192 194 is be VBZ 195 201 intact intact JJ 201 202 , , , 203 206 but but CC 207 210 its its PRP$ 211 212 5 5 CD 212 213 ’ ' SYM 214 226 untranslated untranslated JJ 227 233 region region NN 234 236 is be VBZ 237 245 replaced replace VBN 246 250 with with IN 251 260 sequences sequence NNS 261 265 from from IN 266 269 the the DT 270 283 translocation translocation NN 284 291 partner partner NN 291 292 . . . 293 296 The the DT 297 304 present present JJ 305 310 study study NN 311 316 shows show VBZ 317 321 that that IN 322 327 BCL-6 bcl-6 NN 328 338 expression expression NN 339 341 is be VBZ 342 351 regulated regulate VBN 352 354 in in IN 355 366 lymphocytes lymphocyte NNS 367 373 during during IN 374 383 mitogenic mitogenic JJ 384 395 stimulation stimulation NN 395 396 . . . 397 404 Resting rest VBG 405 406 B B NNP 407 410 and and CC 411 412 T t NN 413 424 lymphocytes lymphocyte NNS 425 432 contain contain VBP 433 437 high high JJ 438 444 levels level NNS 445 447 of of IN 448 453 BCL-6 BCL-6 NNP 454 458 mRNA mRNA NNP 458 459 . . . 460 471 Stimulation stimulation NN 472 474 of of IN 475 480 mouse mouse NN 481 482 B b NN 483 488 cells cell NNS 489 493 with with IN 494 502 anti-IgM anti-igm JJ 503 505 or or CC 506 509 IgD IgD NNP 510 520 antibodies antibody NNS 520 521 , , , 522 531 bacterial bacterial JJ 532 550 lipopolysaccharide lipopolysaccharide NN 550 551 , , , 552 559 phorbol phorbol NN 560 572 12-myristate 12-myristate NN 573 583 13-acetate 13-acetate NN 584 588 plus plus CC 589 598 ionomycin ionomycin NN 598 599 , , , 600 602 or or CC 603 607 CD40 CD40 NNP 608 614 ligand ligand NN 615 618 led lead VBD 619 621 to to TO 622 623 a a DT 624 633 five-fold five-fold JJ 634 636 to to TO 637 644 35-fold 35-fold JJ 645 653 decrease decrease NN 654 656 in in IN 657 662 BCL-6 BCL-6 NNP 663 667 mRNA mRNA NNP 668 674 levels level NNS 674 675 . . . 676 683 Similar similar JJ 684 698 downregulation downregulation NN 699 701 of of IN 702 707 BCL-6 BCL-6 NNP 708 712 mRNA mRNA NNP 713 716 was be VBD 717 721 seen see VBN 722 724 in in IN 725 730 human human JJ 731 732 B B NNP 733 738 cells cell NNS 739 749 stimulated stimulate VBN 750 754 with with IN 755 769 Staphylococcus staphylococcus FW 770 776 aureus aureus FW 777 781 plus plus CC 782 795 interleukin-2 interleukin-2 NN 796 798 or or CC 799 807 anti-IgM anti-igm JJ 808 818 antibodies antibody NNS 819 822 and and CC 823 825 in in IN 826 831 human human JJ 832 833 T t NN 834 845 lymphocytes lymphocyte NNS 846 856 stimulated stimulate VBN 857 861 with with IN 862 880 phytohemagglutinin phytohemagglutinin NN 880 881 . . . 882 887 BCL-6 BCL-6 NNP 888 892 mRNA mRNA NNP 893 899 levels level NNS 900 905 began begin VBD 906 908 to to TO 909 917 decrease decrease VB 918 919 8 8 CD 920 922 to to TO 923 925 16 16 CD 926 931 hours hour NNS 932 937 after after IN 938 949 stimulation stimulation NN 949 950 , , , 951 957 before before IN 958 963 cells cell NNS 964 971 entered enter VBD 972 973 S S NNP 974 979 phase phase NN 979 980 . . . 981 989 Although although IN 990 1000 polyclonal polyclonal JJ 1001 1011 activation activation NN 1012 1014 of of IN 1015 1016 B B NNP 1017 1022 cells cell NNS 1023 1025 in in FW 1026 1031 vitro vitro FW 1032 1042 invariably invariably RB 1043 1052 decreased decrease VBD 1053 1058 BCL-6 BCL-6 NNP 1059 1063 MRNA MRNA NNP 1064 1074 expression expression NN 1074 1075 , , , 1076 1085 activated activate VBN 1086 1087 B B NNP 1088 1093 cells cell NNS 1094 1098 from from IN 1099 1104 human human JJ 1105 1113 germinal germinal JJ 1114 1121 centers center NNS 1122 1131 expressed express VBD 1132 1137 BCL-6 BCL-6 NNP 1138 1142 mRNA mRNA NNP 1143 1145 at at IN 1146 1152 levels level NNS 1153 1163 comparable comparable JJ 1164 1166 to to TO 1167 1170 the the DT 1171 1177 levels level NNS 1178 1180 in in IN 1181 1188 resting rest VBG 1189 1190 B B NNP 1191 1196 cells cell NNS 1196 1197 . . . 1198 1205 Despite despite IN 1206 1211 these these DT 1212 1219 similar similar JJ 1220 1224 mRNA mrna NN 1225 1231 levels level NNS 1231 1232 , , , 1233 1238 BCL-6 BCL-6 NNP 1239 1246 protein protein NN 1247 1257 expression expression NN 1258 1261 was be VBD 1262 1271 threefold threefold RB 1272 1274 to to TO 1275 1282 34-fold 34-fold RB 1283 1289 higher high JJR 1290 1292 in in IN 1293 1301 germinal germinal JJ 1302 1308 center center NN 1309 1310 B b NN 1311 1316 cells cell NNS 1317 1321 than than IN 1322 1324 in in IN 1325 1332 resting rest VBG 1333 1334 B B NNP 1335 1340 cells cell NNS 1340 1341 , , , 1342 1352 suggesting suggest VBG 1353 1357 that that IN 1358 1363 BCL-6 bcl-6 NN 1364 1371 protein protein NN 1372 1378 levels level NNS 1379 1382 are be VBP 1383 1393 controlled control VBN 1394 1396 by by IN 1397 1410 translational translational JJ 1411 1413 or or CC 1414 1431 posttranslational posttranslational JJ 1432 1442 mechanisms mechanism NNS 1442 1443 . . . 1444 1449 These these DT 1450 1462 observations observation NNS 1463 1470 suggest suggest VBP 1471 1475 that that IN 1476 1479 the the DT 1480 1488 germinal germinal JJ 1489 1495 center center NN 1496 1504 reaction reaction NN 1505 1513 provides provide VBZ 1514 1520 unique unique JJ 1521 1531 activation activation NN 1532 1539 signals signal NNS 1540 1542 to to TO 1543 1544 B B NNP 1545 1550 cells cell NNS 1551 1555 that that WDT 1556 1561 allow allow VBP 1562 1565 for for IN 1566 1575 continued continued JJ 1575 1576 , , , 1577 1587 high-level high-level JJ 1588 1593 BCL-6 bcl-6 NN 1594 1604 expression expression NN 1604 1605 . . .