The germinal center in the pathogenesis of B cell lymphomas

Abstract

The adaptive immune system has evolved to allow effective responses against a virtually unlimited number of invading pathogens. This process requires the transient formation of germinal centers (GC), a dynamic environment that ensures the generation and selection of B cells capable to produce antibodies with high antigen affinity, or to maintain the memory of that antigen for life. However, this comes at a cost, as the unique events accompanying the GC reaction pose a significant risk to the genome of B cells, which must endure elevated levels of replication stress, while proliferating at high rates and undergoing DNA breaks introduced by somatic hypermutation and class switch recombination. Indeed, the genetic/epigenetic disruption of programs implicated in normal GC biology has emerged as a hallmark of most B cell lymphomas. This improved understanding provides a conceptual framework for the identification of cellular pathways that could be exploited for precision medicine approaches.

Discovery Science highlights from the 17th International Conference on Malignant Lymphoma

“…Over the years, the work of a multitude of lymphoma researchers together with the emergence of new technologies, have resulted in a richer understanding of the molecular features that initiate and support lymphomagenesis. Laura Pasqualucci (New York, USA), is aptly recognised as having made seminal contributions to our understanding of lymphoma biology and as such, a number of her team's findings featured in her Meet the Professor session, 1 which focused on the role of the germinal center (GC) in the genesis of lymphomas. After giving an authoritative overview of the genetic, epigenetic and microenvironmental perturbations involved in the pathogenesis of lymphomas originating from the GC, she explained how she and Riccardo Dalla‐Favera (New York, USA), embarked on opening the “big black box” that is the non‐coding human genome to better study GC‐derived lymphomas.…”