Transitional B Cells Exhibit a B Cell Receptor-Specific Nuclear Defect in Gene Transcription
Copyright policy )Transitional B Cells Exhibit a B Cell Receptor-Specific Nuclear Defect in Gene Transcription
Abstract 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-κB 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 IκB kinase activation, NF-κB 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-specific “nuclear nonresponsiveness” upon encounter with self-Ags.
- University of Mary United States
- University of Washington United States
Cell Nucleus, Mice, Knockout, Mice, Inbred BALB C, NFATC Transcription Factors, Transcription, Genetic, Cell Survival, B-Lymphocyte Subsets, Models, Immunological, Gene Expression Regulation, Developmental, Receptors, Antigen, B-Cell, Apoptosis, Mice, Transgenic, Minor Histocompatibility Antigens, Proto-Oncogene Proteins c-myc, Mice, Proto-Oncogene Proteins c-bcl-2, Animals, Epitopes, B-Lymphocyte, Cells, Cultured
Cell Nucleus, Mice, Knockout, Mice, Inbred BALB C, NFATC Transcription Factors, Transcription, Genetic, Cell Survival, B-Lymphocyte Subsets, Models, Immunological, Gene Expression Regulation, Developmental, Receptors, Antigen, B-Cell, Apoptosis, Mice, Transgenic, Minor Histocompatibility Antigens, Proto-Oncogene Proteins c-myc, Mice, Proto-Oncogene Proteins c-bcl-2, Animals, Epitopes, B-Lymphocyte, Cells, Cultured
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