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Publication : The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry.

First Author  Dominguez-Sola D Year  2012
Journal  Nat Immunol Volume  13
Issue  11 Pages  1083-91
PubMed ID  23001145 Mgi Jnum  J:188565
Mgi Id  MGI:5441116 Doi  10.1038/ni.2428
Citation  Dominguez-Sola D, et al. (2012) The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry. Nat Immunol 13(11):1083-91
abstractText  After antigenic challenge, B cells enter the dark zone (DZ) of germinal centers (GCs) to proliferate and hypermutate their immunoglobulin genes. Mutants with greater affinity for the antigen are positively selected in the light zone (LZ) to either differentiate into plasma and memory cells or reenter the DZ. The molecular circuits that govern positive selection in the GC are not known. We show here that the GC reaction required biphasic regulation of expression of the cell-cycle regulator c-Myc that involved its transient induction during early GC commitment, its repression by Bcl-6 in DZ B cells and its reinduction in B cells selected for reentry into the DZ. Inhibition of c-Myc in vivo led to GC collapse, which indicated an essential role for c-Myc in GCs. Our results have implications for the mechanism of GC selection and the role of c-Myc in lymphomagenesis.
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