CYCLOSPORINE-A SENSITIVE INDUCTION OF NF-AT IN MURINE B-CELLS

被引:113
作者
VENKATARAMAN, L
FRANCIS, DA
WANG, ZH
LIU, JL
ROTHSTEIN, TL
SEN, R
机构
[1] BRANDEIS UNIV,DEPT BIOL,WALTHAM,MA 02254
[2] BOSTON UNIV,MED CTR,DEPT PATHOL,BOSTON,MA 02118
[3] BOSTON UNIV,MED CTR,DEPT MICROBIOL,BOSTON,MA 02118
[4] BOSTON UNIV,MED CTR,DEPT MED,BOSTON,MA 02118
关键词
D O I
10.1016/1074-7613(94)90097-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Primary B cells are Induced to proliferate by crosslinking surface immunoglobulin or by its pharmacological equivalent, phorbol ester and calcium ionophore. However, nuclear responses that have been studied in activated B cells are typically inducible with phorbol esters alone. We show that a factor, indistinguishable from the nuclear factor of activated T cells (NF-AT), is induced in B cells in response to anti-immunoglobulin signals or the combined action of phorbol ester and ionomycin, but not in response to either reagent alone. The signals necessary for NF-AT induction in B cells, therefore, closely parallel those required to induce B cell proliferation. Transfection analysis shows that B cell NF-AT is a transcriptional activator. Furthermore, NF-AT induction In splenic cells is suppressed by cyclosporin A, suggesting a mechanism by which immunosuppressive agents act on the B cell compartment. We propose that NF-AT should be considered more generally as a nuclear factor of activated lymphoid cells.
引用
收藏
页码:189 / 196
页数:8
相关论文
共 37 条
[1]   THE IMMUNOSUPPRESSANT FK-506 SPECIFICALLY INHIBITS MITOGEN-INDUCED ACTIVATION OF THE INTERLEUKIN-2 PROMOTER AND THE ISOLATED ENHANCER ELEMENTS NFIL-2A AND NF-AT1 [J].
BANERJI, SS ;
PARSONS, JN ;
TOCCI, MJ .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (08) :4074-4087
[2]   2 DISTINCT SIGNAL TRANSMISSION PATHWAYS IN LYMPHOCYTES-T ARE INHIBITED BY COMPLEXES FORMED BETWEEN AN IMMUNOPHILIN AND EITHER FK506 OR RAPAMYCIN [J].
BIERER, BE ;
MATTILA, PS ;
STANDAERT, RF ;
HERZENBERG, LA ;
BURAKOFF, SJ ;
CRABTREE, G ;
SCHREIBER, SL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (23) :9231-9235
[3]   THE NFAT-1 DNA-BINDING COMPLEX IN ACTIVATED T-CELLS CONTAINS FRA-1 AND JUNB [J].
BOISE, LH ;
PETRYNIAK, B ;
MAO, XH ;
JUNE, CH ;
WANG, CY ;
LINDSTEN, T ;
BRAVO, R ;
KOVARY, K ;
LEIDEN, JM ;
THOMPSSON, CB .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (03) :1911-1919
[4]  
CHILES TC, 1992, J IMMUNOL, V149, P825
[5]  
CHILES TC, 1991, J IMMUNOL, V146, P1730
[6]   IDENTIFICATION OF CALCINEURIN AS A KEY SIGNALING ENZYME IN LYMPHOCYTE-T ACTIVATION [J].
CLIPSTONE, NA ;
CRABTREE, GR .
NATURE, 1992, 357 (6380) :695-697
[7]   CHARACTERIZATION OF ANTIGEN RECEPTOR RESPONSE ELEMENTS WITHIN THE INTERLEUKIN-2 ENHANCER [J].
DURAND, DB ;
SHAW, JP ;
BUSH, MR ;
REPLOGLE, RE ;
BELAGAJE, R ;
CRABTREE, GR .
MOLECULAR AND CELLULAR BIOLOGY, 1988, 8 (04) :1715-1724
[8]   CYCLOSPORINE-A SPECIFICALLY INHIBITS FUNCTION OF NUCLEAR PROTEINS INVOLVED IN T-CELL ACTIVATION [J].
EMMEL, EA ;
VERWEIJ, CL ;
DURAND, DB ;
HIGGINS, KM ;
LACY, E ;
CRABTREE, GR .
SCIENCE, 1989, 246 (4937) :1617-1620
[9]   NUCLEAR-ASSOCIATION OF A T-CELL TRANSCRIPTION FACTOR BLOCKED BY FK-506 AND CYCLOSPORINE-A [J].
FLANAGAN, WM ;
CORTHESY, B ;
BRAM, RJ ;
CRABTREE, GR .
NATURE, 1991, 352 (6338) :803-807
[10]   MULTIPLE PROTEIN-BINDING SITES IN THE 5'-FLANKING REGION REGULATE C-FOS EXPRESSION [J].
GILMAN, MZ ;
WILSON, RN ;
WEINBERG, RA .
MOLECULAR AND CELLULAR BIOLOGY, 1986, 6 (12) :4305-4316