0 2 An an DT 3 9 active active JJ 10 15 v-abl v-abl JJ 16 23 protein protein NN 24 32 tyrosine tyrosine NN 33 39 kinase kinase NNP 40 46 blocks block VBZ 47 61 immunoglobulin immunoglobulin NN 62 73 light-chain light-chain JJ 74 78 gene gene NN 79 92 rearrangement rearrangement NN 92 93 . . . 95 103 Lymphoid lymphoid JJ 104 109 cells cell NNS 110 121 transformed transform VBN 122 124 by by IN 125 132 Abelson Abelson NNP 133 139 murine murine JJ 140 148 leukemia leukemia NN 149 154 virus virus NN 155 159 have have VBP 160 168 provided provide VBN 169 172 one one CD 173 175 of of IN 176 179 the the DT 180 187 classic classic JJ 188 194 models model NNS 195 198 for for IN 199 204 study study NN 205 207 of of IN 208 213 early early JJ 214 220 B-cell b-cell NN 221 232 development development NN 233 236 and and CC 237 251 immunoglobulin immunoglobulin NN 252 265 rearrangement rearrangement NN 265 266 . . . 267 271 Most most JJS 272 274 of of IN 275 280 these these DT 281 286 cells cell NNS 287 291 have have VBP 292 302 rearranged rearrange VBN 303 308 their their PRP$ 309 320 heavy-chain heavy-chain JJ 321 326 locus locus NN 327 330 but but CC 331 334 not not RB 335 340 their their PRP$ 341 346 light light JJ 347 352 chain chain NN 353 358 genes gene NNS 358 359 , , , 360 370 suggesting suggest VBG 371 375 that that IN 376 378 an an DT 379 385 active active JJ 386 391 v-abl v-abl JJ 392 399 protein protein NN 400 410 interferes interfere VBZ 411 415 with with IN 416 420 this this DT 421 436 differentiation differentiation NN 437 441 step step NN 441 442 . . . 443 445 To to TO 446 450 test test VB 451 455 this this DT 456 466 hypothesis hypothesis NN 466 467 , , , 468 479 light-chain light-chain JJ 480 484 gene gene NN 485 494 structure structure NN 495 498 was be VBD 499 507 examined examine VBN 508 510 in in IN 511 516 pre-B pre-b JJ 517 522 cells cell NNS 523 534 transformed transform VBN 535 537 by by IN 538 559 temperature-sensitive temperature-sensitive JJ 560 567 mutants mutant NNS 568 570 of of IN 571 574 the the DT 575 582 Abelson Abelson NNP 583 588 virus virus NN 589 592 and and CC 593 595 in in IN 596 607 derivatives derivative NNS 608 612 that that WDT 613 620 survive survive VBP 621 623 at at IN 624 627 the the DT 628 641 nonpermissive nonpermissive JJ 642 653 temperature temperature NN 654 661 because because IN 662 666 they they PRP 667 674 express express VBP 675 676 a a DT 677 682 human human JJ 683 688 BCL-2 bcl-2 NN 689 693 gene gene NN 693 694 . . . 695 698 Our our PRP$ 699 706 studies study NNS 707 713 reveal reveal VBP 714 718 that that IN 719 731 inactivation inactivation NN 732 734 of of IN 735 738 the the DT 739 744 v-abl v-abl JJ 745 752 protein protein NN 753 761 tyrosine tyrosine NN 762 768 kinase kinase NNP 769 777 triggers trigger VBZ 778 792 high-frequency high-frequency NN 793 806 rearrangement rearrangement NN 807 809 of of IN 810 815 kappa kappa NN 816 819 and and CC 820 826 lambda lambda NN 827 838 light-chain light-chain JJ 839 844 genes gene NNS 844 845 . . . 846 851 These these DT 852 858 events event NNS 859 862 are be VBP 863 874 accompanied accompany VBN 875 877 by by IN 878 884 marked marked JJ 885 894 increases increase NNS 895 897 in in IN 898 901 the the DT 902 912 expression expression NN 913 915 of of IN 916 921 RAG-1 rag-1 NN 922 925 and and CC 926 931 RAG-2 rag-2 NN 932 936 RNAs rna NNS 936 937 . . . 938 943 These these DT 944 953 increases increase NNS 954 959 occur occur VBP 960 962 in in IN 963 966 the the DT 967 974 absence absence NN 975 977 of of IN 978 985 protein protein NN 986 995 synthesis synthesis NN 996 999 but but CC 1000 1003 are be VBP 1004 1013 dependent dependent JJ 1014 1016 on on IN 1017 1029 inactivation inactivation NN 1030 1032 of of IN 1033 1036 the the DT 1037 1042 v-abl v-abl JJ 1043 1050 protein protein NN 1051 1059 tyrosine tyrosine NN 1060 1066 kinase kinase NNP 1066 1067 . . . 1068 1070 As as IN 1071 1081 documented document VBN 1082 1084 in in IN 1085 1088 the the DT 1089 1101 accompanying accompany VBG 1102 1107 paper paper NN 1108 1109 ( ( ( 1109 1113 Klug Klug NNP 1114 1116 et et FW 1117 1120 al. al. FW 1120 1121 , , , 1122 1126 this this DT 1127 1132 issue issue NN 1132 1133 ) ) ) 1133 1134 , , , 1135 1137 an an DT 1138 1144 active active JJ 1145 1150 v-abl v-abl JJ 1151 1158 protein protein NN 1159 1163 also also RB 1164 1174 suppresses suppress VBZ 1175 1178 the the DT 1179 1187 activity activity NN 1188 1190 of of IN 1191 1199 NF-kappa NF-kappa NNP 1200 1205 B/rel B/rel NNP 1206 1209 and and CC 1210 1220 expression expression NN 1221 1231 controlled control VBN 1232 1234 by by IN 1235 1238 the the DT 1239 1244 kappa kappa NN 1245 1251 intron intron NN 1252 1260 enhancer enhancer NN 1260 1261 . . . 1262 1270 Together together RB 1271 1276 these these DT 1277 1281 data datum NNS 1282 1293 demonstrate demonstrate VBP 1294 1298 that that IN 1299 1302 the the DT 1303 1308 v-abl v-abl JJ 1309 1316 protein protein NN 1317 1329 specifically specifically RB 1330 1340 interferes interfere VBZ 1341 1345 with with IN 1346 1357 light-chain light-chain JJ 1358 1362 gene gene NN 1363 1376 rearrangement rearrangement NN 1377 1379 by by IN 1380 1391 suppressing suppress VBG 1392 1394 at at IN 1395 1400 least least JJS 1401 1404 two two CD 1405 1413 pathways pathway NNS 1414 1423 essential essential JJ 1424 1427 for for IN 1428 1432 this this DT 1433 1438 stage stage NN 1439 1441 of of IN 1442 1448 B-cell b-cell NN 1449 1464 differentiation differentiation NN 1465 1468 and and CC 1469 1476 suggest suggest VBP 1477 1481 that that IN 1482 1490 tyrosine tyrosine NN 1491 1506 phosphorylation phosphorylation NN 1507 1509 is be VBZ 1510 1519 important important JJ 1520 1522 in in IN 1523 1533 regulating regulate VBG 1534 1537 RAG RAG NNP 1538 1542 gene gene NN 1543 1553 expression expression NN 1553 1554 . . .