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A Transcriptional Regulatory Switch Underlying B-Cell Terminal Differentiation and its Disruption by Dioxin
Citation:
Bhattacharya, S., R. CONOLLY, M. E. Andersen, AND Q. Zhang. A Transcriptional Regulatory Switch Underlying B-Cell Terminal Differentiation and its Disruption by Dioxin. Presented at Institue for Mathematics and Its Applications Workshop, Minneapolis, MN, April 21 - 25, 2008.
Impact/Purpose:
The terminal differentiation of B lymphocytes into antibody-secreting plasma cells upon antigen stimulation is a crucial step in the humoral immune response. The mutually-repressive interactions among three key regulatory transcription factors underlying B to plasma cell differentiation, Bcl-6, Blimp-1 and Pax5, give rise to double-negative feedback loops – a common design “motif” in the transcriptional regulatory networks underlying binary cell fate choice in the hematopoietic stem cell (HSC) lineage. The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with the immune response by suppressing the formation of antibody-secreting plasma cells. A bistable switch arising from the coupled double-negative feedback loops involving Bcl-6, Blimp-1 and Pax5 forms the basis of the B-cell to plasma cell differentiation program and its disruption by dioxin .
Description:
The terminal differentiation of B lymphocytes into antibody-secreting plasma cells upon antigen stimulation is a crucial step in the humoral immune response. The mutually-repressive interactions among three key regulatory transcription factors underlying B to plasma cell differentiation, Bcl-6, Blimp-1 and Pax5, give rise to double-negative feedback loops – a common design “motif” in the transcriptional regulatory networks underlying binary cell fate choice in the hematopoietic stem cell (HSC) lineage. The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with the immune response by suppressing the formation of antibody-secreting plasma cells. A bistable switch arising from the coupled double-negative feedback loops involving Bcl-6, Blimp-1 and Pax5 forms the basis of the B-cell to plasma cell differentiation program and its disruption by dioxin .