The Role of Epigenetic Mechanisms in B Cell Lymphoma Pathogenesis

Abstract

The capacity of the adaptive immune system to respond to antigenic challenges relies on rapid diversification, expansion, and functional specialization of mature B cells. To accomplish this, activated B cells are transiently endowed with phenotypes that would normally be suppressed in somatic cells, such as enhanced proliferative potential and tolerance for genomic instability. Acquisition of these traits, directed by immune signaling cues and orchestrated by transcriptional and epigenetic programs, sets the stage for malignant transformation, often due to somatic mutations targeting epigenetic machinery in B cell lymphomas. This review examines how such mutations hack the epigenome to reprogram the immune response in such a way as to facilitate the emergence of malignant traits, suppress immune surveillance, and ultimately drive transformation and progression of a diverse spectrum of B cell lymphomas. Importantly, these novel mechanisms reveal vulnerabilities that can be harnessed using new forms of epigenetic therapy. Expected final online publication date for the Annual Review of Cancer Biology, Volume 5 is March 4, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Epigenetic regulation of B cells and its role in autoimmune pathogenesis

“…Deletion of a GC-specific region upstream of Bcl6 that shows frequent intrachromosomal interactions results in diminished GC formation without affecting other developmental stages [ 53 ]. Furthermore, dysregulated epigenetic regulation of BCL6 in B cells is associated with GC-derived lymphoma [ 56 ]. T follicular helper (Tfh) cells, characterized by high expression of BCL6, play an essential role in the GC reaction and autoimmune pathogenesis [ 3 ].…”