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Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program

ABSTRACT: Heirarchical development of B-cells involves the induction and supression of large sets of genes that provide the basis for differentiation and, ultimately, antibody production. We used microarrays to define comprehensive differentiation state-specific transcriptional signatures in order to gain insight into B-cell biology. In addition, we compared profiles of normal B-cells to those of murine lymphoma models that are putatively aligned with different states. B-cells of different differentiation states were purified from the bone marrow and spleen of mice use flow cytometry with antibodies specific for pre-defined markers of each differentiation state. Purified populations were then profiled using Affymetrix Mouse 430A2 gene expression microarrays. Tumors from Bcl6-trangenic mice, Bcl6/Myc dual-transgenic mice and p53/Lig4 double knock-out mice were also profiled using these microarrays in order to assess the similarities/differences between normal and malignant B-cells.

ORGANISM(S): Mus musculus

SUBMITTER: Michael Green 

PROVIDER: E-GEOD-26408 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program.

Green Michael R MR   Monti Stefano S   Dalla-Favera Riccardo R   Pasqualucci Laura L   Walsh Nicole C NC   Schmidt-Supprian Marc M   Kutok Jeffery L JL   Rodig Scott J SJ   Neuberg Donna S DS   Rajewsky Klaus K   Golub Todd R TR   Alt Frederick W FW   Shipp Margaret A MA   Manis John P JP  

Proceedings of the National Academy of Sciences of the United States of America 20110131 7

We utilized gene expression profiling of a comprehensive panel of purified developmentally defined normal murine B cells to identify unique transcriptional signatures for each subset. To elucidate transcription factor activities that function in a stage-specific fashion, we used gene sets that share transcription factor targets and found that germinal center B cells had a robust enrichment of up-regulated and down-regulated signatures compared with the other B-cell subsets. Notably, we found Yy1  ...[more]

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