%0 Journal Article %1 Sciammas2011Incoherent %A Sciammas, Roger %A Li, Ying %A Warmflash, Aryeh %A Song, Yiqiang %A Dinner, Aaron R. %A Singh, Harinder %D 2011 %I Nature Publishing Group %J Molecular Systems Biology %K immune-system transcriptional-regulatory-network %R 10.1038/msb.2011.25 %T An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling %U http://dx.doi.org/10.1038/msb.2011.25 %V 7 %X The B-lymphocyte lineage is a leading system for analyzing gene regulatory networks (GRNs) that orchestrate distinct cell fate transitions. Upon antigen recognition, B cells can diversify their immunoglobulin (Ig) repertoire via somatic hypermutation (SHM) and/or class switch DNA recombination (CSR) before differentiating into antibody-secreting plasma cells. We construct a mathematical model for a GRN underlying this developmental dynamic. The intensity of signaling through the Ig receptor is shown to control the bimodal expression of a pivotal transcription factor, IRF-4, which dictates B cell fate outcomes. Computational modeling coupled with experimental analysis supports a model of 'kinetic control', in which B cell developmental trajectories pass through an obligate transient state of variable duration that promotes diversification of the antibody repertoire by SHM/CSR in direct response to antigens. More generally, this network motif could be used to translate a morphogen gradient into developmental inductive events of varying time, thereby enabling the specification of distinct cell fates.

@article{Sciammas2011Incoherent, abstract = {The B-lymphocyte lineage is a leading system for analyzing gene regulatory networks ({GRNs}) that orchestrate distinct cell fate transitions. Upon antigen recognition, B cells can diversify their immunoglobulin (Ig) repertoire via somatic hypermutation ({SHM}) and/or class switch {DNA} recombination ({CSR}) before differentiating into antibody-secreting plasma cells. We construct a mathematical model for a {GRN} underlying this developmental dynamic. The intensity of signaling through the Ig receptor is shown to control the bimodal expression of a pivotal transcription factor, {IRF}-4, which dictates B cell fate outcomes. Computational modeling coupled with experimental analysis supports a model of 'kinetic control', in which B cell developmental trajectories pass through an obligate transient state of variable duration that promotes diversification of the antibody repertoire by {SHM}/{CSR} in direct response to antigens. More generally, this network motif could be used to translate a morphogen gradient into developmental inductive events of varying time, thereby enabling the specification of distinct cell fates.}, added-at = {2018-12-02T16:09:07.000+0100}, author = {Sciammas, Roger and Li, Ying and Warmflash, Aryeh and Song, Yiqiang and Dinner, Aaron R. and Singh, Harinder}, biburl = {https://www.bibsonomy.org/bibtex/2cf11530bef280dfc614be6b9181fc5b8/karthikraman}, citeulike-article-id = {9351296}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/msb.2011.25}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/msb201125}, day = 24, doi = {10.1038/msb.2011.25}, interhash = {90e0f7b3526d1c5b1f39a28acb186af5}, intrahash = {cf11530bef280dfc614be6b9181fc5b8}, journal = {Molecular Systems Biology}, keywords = {immune-system transcriptional-regulatory-network}, month = may, posted-at = {2011-05-31 05:25:03}, priority = {2}, publisher = {Nature Publishing Group}, timestamp = {2018-12-02T16:09:07.000+0100}, title = {An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling}, url = {http://dx.doi.org/10.1038/msb.2011.25}, volume = 7, year = 2011 }