Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 5, Pages 2868-2878Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0802368
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Funding
- Cancer Research Institute Training Grant
- National Institutes of Health [HD37091, CA81140]
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The signaling programs that enforce negative selection in early transitional (T1) B cells in response to BCR engagement remain poorly defined. We conducted a comprehensive comparison of BCR signaling in T1 vs follicular mature splenic B cells. T1, in contrast to follicular mature B cells, failed to express key NF-kappa B target genes in response to BCR engagement and exhibited a striking defect in assembly of an active transcriptional complex at the promoter of the survival and proliferative genes A1 and c-Myc. Surprisingly, and contrary to previous models, classical protein kinase C and I kappa B kinase activation, NF-kappa B nuclear translocation and DNA binding were intact in T1 B cells. Furthermore, despite a marked reduction in NFAT1 expression, differential NFAT or AP-1 activation cannot explain this transcriptional defect. Our combined findings demonstrate that T1 B cells are programmed for signal- and stage-specitic nuclear nonresponsiveness upon encounter with self-Ags. The Journal of Immunology, 2009, 182: 2868-2878.
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