Different nuclear signals are activated by the B cell receptor during positive versus negative signaling

被引:327
作者
Healy, JI
Dolmetsch, RE
Timmerman, LA
Cyster, JG
Thomas, ML
Crabtree, GR
Lewis, RS
Goodnow, CC
机构
[1] STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305
[2] STANFORD UNIV,SCH MED,PROGRAM IMMUNOL,STANFORD,CA 94305
[3] STANFORD UNIV,SCH MED,DEPT MOL & CELLULAR PHYSIOL,STANFORD,CA 94305
[4] STANFORD UNIV,SCH MED,HOWARD HUGHES MED INST,STANFORD,CA 94305
[5] WASHINGTON UNIV,SCH MED,DEPT PATHOL,HOWARD HUGHES MED INST,ST LOUIS,MO 63110
关键词
D O I
10.1016/S1074-7613(00)80285-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
It is not known how immunogenic versus tolerogenic cellular responses are signaled by receptors such as the B cell antigen receptor (BCR). Here we compare BCR signaling in naive cells that respond positively to foreign antigen and self-tolerant cells that respond negatively to self-antigen. In naive cells, foreign antigen triggered a Targe biphasic calcium response and activated nuclear signals through NF-AT, NF-kappa B, JNK, and ERK/pp90rsk. In tolerant B cells, self-antigen stimulated low calcium oscillations and activated NF-AT and ERK/pp90rsk but not NF-kappa B or JNK. Self-reactive B cells lacking the phosphatase CD45 did not exhibit calcium oscillations or ERK/pp90rsk activation, nor did they repond negatively to self-antigen. These data reveal striking biochemical differences in BCR signaling to the nucleus during positive selection by foreign antigens and negative selection by self-antigens.
引用
收藏
页码:419 / 428
页数:10
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