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.
At a glance
Gene Expression Omnibus
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- Supplementary Text and Figures (4M)
Supplementary Figures 1–7 and Tables 4–6
- Supplementary Table 1 (53K)
BCL6 ChIP-on-chip binding profile across the proximal region of the MYC locus.
- Supplementary Table 2 (33K)
GFPMYC signature genes.
- Supplementary Table 3 (25K)
Gene Set Enrichment Analysis of GFPMYC signatures.
- Supplementary Table 7 (53K)
List of primers used in real-time quantitative RT-PCR (qRT-PCR), quantitative chromatin immunoprecipitation (qChIP) and IgH-V gene sequence analysis.