Thursday 6 Th October at 1.30pm, room P. Druet
Dr. Rinako Nakagawa – Francis Crick Institute
Germinal centres (GC) form in secondary lymphoid organs upon infection and immunisation. The microstructures are essential sites for the production of high-affinity antibody-secreting plasma cells. GCs are anatomically divided into two regions, the dark zone (DZ) and the light zone (LZ). For the diversification of antibodies, GCs positively select ‘fit’ cells in the LZ. These positively selected GC-B cells migrate from the LZ to the DZ and dynamically change their transcriptional programs for distinct functions suited to the zone while coping with differential oxygen availability between the zones. GC-B cells are fast-dividing; thus, multi-layered gene regulations are required to prevent genome instability that may cause malignant transformation. MicroRNAs (miR)s are small non-coding RNAs and serve as critical players in GC maintenance. MiRs post-transcriptionally regulate their target genes and hence can swiftly repress gene expression. Among those, miR-155 is essential for GC maintenance and is mainly expressed in positively selected GC-B cells. However, it remains unknown the extent to which DZ – LZ transition in gene expression profiles is regulated by miR-155.
We have recently found that transcriptional programs are critically modulated at the epigenetic level downstream of miR-155 function. MiR-155-mediated epigenetic modulation controls the proliferation and survival of positively selected GC-B cells in the hypoxic LZ environment and enables replenishment of DZ GC-B cells.
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