The ubiquitin system in normal and infected germinal center B cells.

The ubiquitin system is a highly regulated cellular mechanism that plays a central role in germinal center (GC) B cells, essential for protective humoral immunity and the site of gammaherpesvirus latency establishment. GC B cells undergo extraordinary levels of proliferation, DNA damage, and apoptosis prior to differentiating to long-lived memory or plasma cells, and ubiquitin pathways underpin these activities. Oncogenic gammaherpesviruses infect B cells and drive them through a GC activation program. Viral programs exploit ubiquitin biology to establish latency in GC B cells and persist for life in long-lived memory B cells, poised to drive lymphomagenesis over time. Here, we will first define how ubiquitin regulates normal GC B cells. Within this framework, we will describe how gammaherpesviruses interact with these mechanisms to establish latency, highlighting common and divergent mechanisms of GC control in infected and normal B cells. Further understanding ubiquitin mechanisms in GC B cells will aid the discovery of highly specific molecular circuits that regulate B-cell fate and function, with broad relevance to antiviral immunity and cancer biology.