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.

The germinal center in the pathogenesis of B cell lymphomas

Pasqualucci, Laura
2023

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.
2023
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1566600
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