0 12 Transforming transform VBG 13 19 growth growth NN 20 31 factor-beta factor-beta NN 32 42 suppresses suppress VBZ 43 48 human human JJ 49 50 B B NNP 51 61 lymphocyte lymphocyte NN 62 64 Ig ig NN 65 75 production production NN 76 78 by by IN 79 89 inhibiting inhibit VBG 90 99 synthesis synthesis NN 100 103 and and CC 104 107 the the DT 108 114 switch switch NN 115 119 from from IN 120 123 the the DT 124 132 membrane membrane NN 133 137 form form NN 138 140 to to TO 141 144 the the DT 145 153 secreted secrete VBN 154 158 form form NN 159 161 of of IN 162 164 Ig Ig NNP 165 169 mRNA mRNA NNP 169 170 . . . 172 184 Transforming transform VBG 185 191 growth growth NN 192 203 factor-beta factor-beta NN 204 205 ( ( ( 205 213 TGF-beta TGF-beta NNP 213 214 ) ) ) 215 223 inhibits inhibit VBZ 224 225 B B NNP 226 230 cell cell NN 231 233 Ig ig NN 234 243 secretion secretion NN 244 247 and and CC 248 255 reduces reduce VBZ 256 257 B B NNP 258 262 cell cell NN 263 271 membrane membrane NN 272 274 Ig ig NN 275 285 expression expression NN 285 286 . . . 287 290 The the DT 291 299 addition addition NN 300 302 of of IN 303 311 TGF-beta TGF-beta NNP 312 314 to to TO 315 320 human human JJ 321 322 B B NNP 323 333 lymphocyte lymphocyte NN 334 342 cultures culture NNS 343 353 stimulated stimulate VBN 354 358 with with IN 359 373 Staphylococcus staphylococcus FW 374 380 aureus aureus FW 381 386 Cowan Cowan NNP 387 393 strain strain NN 394 395 I i CD 396 399 and and CC 400 404 IL-2 IL-2 NNP 405 415 completely completely RB 416 425 inhibited inhibit VBD 426 427 B B NNP 428 432 cell cell NN 433 435 Ig ig NN 436 445 secretion secretion NN 446 447 ( ( ( 447 454 greater great JJR 455 459 than than IN 460 462 90 90 CD 462 463 % % NN 463 464 ) ) ) 465 468 and and CC 469 478 decreased decrease VBD 479 480 B B NNP 481 485 cell cell NN 486 493 surface surface NN 494 497 IgM IgM NNP 497 498 , , , 499 502 IgD IgD NNP 502 503 , , , 504 509 kappa kappa NN 510 511 L L NNP 512 517 chain chain NN 517 518 , , , 519 522 and and CC 523 529 lambda lambda NNP 530 531 L L NNP 532 537 chain chain NN 538 548 expression expression NN 548 549 . . . 550 552 In in IN 553 561 contrast contrast NN 561 562 , , , 563 571 TGF-beta TGF-beta NNP 572 575 had have VBD 576 580 only only RB 581 588 minimal minimal JJ 589 596 effects effect NNS 597 599 on on IN 600 603 two two CD 604 609 other other JJ 610 611 B B NNP 612 616 cell cell NN 617 625 membrane membrane NN 626 634 proteins protein NNS 634 635 , , , 636 642 HLA-DR HLA-DR NNP 643 646 and and CC 647 651 CD20 CD20 NNP 651 652 . . . 653 661 Internal internal JJ 662 670 labeling labeling NN 671 675 with with IN 676 677 [ [ ( 677 691 35S]methionine 35S]methionine NNP 692 695 and and CC 696 715 immunoprecipitation immunoprecipitation NN 716 720 with with IN 721 729 anti-IgM anti-igm JJ 729 730 , , , 731 741 anti-kappa anti-kappa JJ 741 742 , , , 743 746 and and CC 747 758 anti-lambda anti-lambda JJ 759 769 antibodies antibody NNS 770 778 revealed reveal VBD 779 780 a a DT 781 789 striking striking JJ 790 799 reduction reduction NN 800 802 in in IN 803 808 kappa kappa NN 809 810 L L NNP 811 816 chain chain NN 817 819 in in IN 820 823 the the DT 824 832 presence presence NN 833 835 of of IN 836 844 TGF-beta TGF-beta NNP 844 845 . . . 846 847 A a DT 848 852 less less RBR 853 863 pronounced pronounced JJ 864 873 reduction reduction NN 874 876 in in IN 877 883 lambda lambda NNP 884 885 L L NNP 886 891 chain chain NN 892 895 and and CC 896 902 microH microh NN 903 908 chain chain NN 909 912 was be VBD 913 917 also also RB 918 923 noted note VBN 923 924 . . . 925 933 Northern Northern NNP 934 938 blot blot NN 939 947 analysis analysis NN 948 950 of of IN 951 954 RNA RNA NNP 955 963 purified purify VBN 964 968 from from IN 969 970 B B NNP 971 976 cells cell NNS 977 984 treated treat VBN 985 989 with with IN 990 998 TGF-beta TGF-beta NNP 999 1002 for for IN 1003 1010 varying vary VBG 1011 1015 time time NN 1016 1025 intervals interval NNS 1026 1034 revealed reveal VBD 1035 1036 a a DT 1037 1048 significant significant JJ 1049 1057 decrease decrease NN 1058 1060 in in IN 1061 1067 steady steady JJ 1068 1073 state state NN 1074 1079 kappa kappa NN 1080 1083 and and CC 1084 1090 lambda lambda NN 1091 1092 L L NNP 1093 1098 chain chain NN 1099 1103 mRNA mrna NN 1104 1110 levels level NNS 1110 1111 . . . 1112 1123 Furthermore furthermore RB 1123 1124 , , , 1125 1126 a a DT 1127 1138 significant significant JJ 1139 1147 decrease decrease NN 1148 1150 in in IN 1151 1154 the the DT 1155 1161 switch switch NN 1162 1166 from from IN 1167 1170 the the DT 1171 1179 membrane membrane NN 1180 1185 forms form NNS 1186 1188 of of IN 1189 1191 mu mu NN 1192 1195 and and CC 1196 1201 gamma gamma NN 1202 1204 to to TO 1205 1210 their their PRP$ 1211 1221 respective respective JJ 1222 1230 secreted secreted JJ 1231 1236 forms form NNS 1237 1240 was be VBD 1241 1246 noted note VBN 1247 1249 in in IN 1250 1253 the the DT 1254 1262 presence presence NN 1263 1265 of of IN 1266 1274 TGF-beta TGF-beta NNP 1274 1275 . . . 1276 1283 Nuclear nuclear JJ 1284 1290 run-on run-on JJ 1291 1302 experiments experiment NNS 1303 1315 demonstrated demonstrate VBD 1316 1325 decreased decrease VBN 1326 1339 transcription transcription NN 1340 1342 of of IN 1343 1348 kappa kappa NN 1349 1350 L L NNP 1351 1356 chain chain NN 1356 1357 . . . 1358 1361 The the DT 1362 1369 effects effect NNS 1370 1372 of of IN 1373 1381 TGF-beta TGF-beta NNP 1382 1384 on on IN 1385 1388 two two CD 1389 1404 transcriptional transcriptional JJ 1405 1415 regulatory regulatory JJ 1416 1423 factors factor NNS 1423 1424 , , , 1425 1430 Oct-2 oct-2 NN 1431 1434 and and CC 1435 1442 nuclear nuclear JJ 1443 1449 factor factor NN 1450 1451 ( ( ( 1451 1453 NF NF NNP 1453 1454 ) ) ) 1455 1460 kappa kappa NN 1461 1462 B B NNP 1462 1463 , , , 1464 1469 known know VBN 1470 1472 to to TO 1473 1475 be be VB 1476 1485 important important JJ 1486 1488 in in IN 1489 1491 Ig ig NN 1492 1496 gene gene NN 1497 1510 transcription transcription NN 1511 1515 were be VBD 1516 1524 examined examine VBN 1524 1525 . . . 1526 1531 Oct-2 oct-2 NN 1532 1536 mRNA mrna NN 1537 1543 levels level NNS 1544 1547 and and CC 1548 1552 both both CC 1553 1558 Oct-2 oct-2 NN 1559 1562 and and CC 1563 1571 NF-kappa NF-kappa NNP 1572 1573 B B NNP 1574 1582 proteins protein NNS 1583 1585 in in IN 1586 1593 nuclear nuclear JJ 1594 1602 extracts extract NNS 1603 1607 were be VBD 1608 1611 not not RB 1612 1619 altered alter VBN 1620 1622 by by IN 1623 1632 treatment treatment NN 1633 1637 with with IN 1638 1646 TGF-beta TGF-beta NNP 1646 1647 . . . 1648 1650 In in IN 1651 1659 contrast contrast NN 1659 1660 , , , 1661 1667 levels level NNS 1668 1670 of of IN 1671 1674 the the DT 1675 1690 transcriptional transcriptional JJ 1691 1697 factor factor NN 1698 1702 AP-1 ap-1 NN 1702 1703 , , , 1704 1709 which which WDT 1710 1712 is be VBZ 1713 1716 not not RB 1717 1722 known know VBN 1723 1725 to to TO 1726 1728 be be VB 1729 1738 important important JJ 1739 1741 in in IN 1742 1743 B B NNP 1744 1748 cell cell NN 1749 1751 Ig ig NN 1752 1762 production production NN 1762 1763 , , , 1764 1768 were be VBD 1769 1776 reduced reduce VBN 1777 1779 by by IN 1780 1788 TGF-beta TGF-beta NNP 1788 1789 . . . 1790 1795 These these DT 1796 1804 findings finding NNS 1805 1816 demonstrate demonstrate VBP 1817 1821 that that IN 1822 1830 TGF-beta TGF-beta NNP 1831 1840 decreases decrease VBZ 1841 1842 B B NNP 1843 1853 lymphocyte lymphocyte NN 1854 1856 Ig ig NN 1857 1866 secretion secretion NN 1867 1869 by by IN 1870 1880 inhibiting inhibit VBG 1881 1884 the the DT 1885 1894 synthesis synthesis NN 1895 1897 of of IN 1898 1900 Ig Ig NNP 1901 1905 mRNA mRNA NNP 1906 1909 and and CC 1910 1920 inhibiting inhibit VBG 1921 1924 the the DT 1925 1931 switch switch NN 1932 1936 from from IN 1937 1940 the the DT 1941 1949 membrane membrane NN 1950 1954 form form NN 1955 1957 to to TO 1958 1961 the the DT 1962 1970 secreted secrete VBN 1971 1976 forms form NNS 1977 1979 of of IN 1980 1982 mu mu NN 1983 1986 and and CC 1987 1992 gamma gamma NN 1993 1997 mRNA mrna NN 1997 1998 . . . 1999 2002 The the DT 2003 2012 mechanism mechanism NN 2013 2015 by by IN 2016 2021 which which WDT 2022 2030 TGF-beta TGF-beta NNP 2031 2039 inhibits inhibit VBZ 2040 2042 Ig ig NN 2043 2048 chain chain NN 2049 2058 synthesis synthesis NN 2059 2061 is be VBZ 2062 2069 unclear unclear JJ 2070 2078 although although IN 2079 2081 it it PRP 2082 2086 does do VBZ 2087 2090 not not RB 2091 2098 involve involve VB 2099 2109 inhibition inhibition NN 2110 2112 of of IN 2113 2116 the the DT 2117 2124 binding binding NN 2125 2127 of of IN 2128 2136 NF-kappa NF-kappa NNP 2137 2138 B B NNP 2139 2141 or or CC 2142 2147 Oct-2 oct-2 NN 2148 2150 to to TO 2151 2156 their their PRP$ 2157 2167 respective respective JJ 2168 2174 target target NN 2175 2184 sequences sequence NNS 2184 2185 . . .