A bistable switch underlying B-cell differentiation and its disruption by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin.

ABSTRACT: The differentiation of B cells into antibody-secreting plasma cells upon antigen stimulation, a crucial step in the humoral immune response, is disrupted by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Several key regulatory proteins in the B-cell transcriptional network have been identified, with two coupled mutually repressive feedback loops among the three transcription factors B-cell lymphoma 6 (Bcl-6), B lymphocyte-induced maturation protein 1(Blimp-1), and paired box 5 (Pax5) forming the core of the network. However, the precise mechanisms underlying B-cell differentiation and its disruption by TCDD are not fully understood. Here we show with a computational systems biology model that coupling of the two feedback loops at the Blimp-1 node, through parallel inhibition of Blimp-1 gene a

SUBMITTER: Bhattacharya S 

PROVIDER: S-EPMC2855357 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature