Factors associated with attendee adherence to COVID-19 guidance during the 2021 DCMS Events Research Programme Phase 1

As part of the DCMS Events Research Programme 2021, we surveyed and interviewed attendees of the FA Cup Semi-Final (18th April), Carabao Cup Final (25th April), the FA Cup Final (15th May), the Snooker World Championship (17th April – 3rd May) and Sefton Park music event (2nd May) to examine attendee experiences of the events, perceptions of the COVID-19 guidance, and factors most associated with self-reported adherence

Somatic hypermutation as a generator of antinuclear antibodies in a murine model of systemic autoimmunity

Systemic lupus erythematosus (SLE) is characterized by high-avidity IgG antinuclear antibodies (ANAs) that are almost certainly products of T cell–dependent immune responses. Whether critical amino acids in the third complementarity-determining region (CDR3) of the ANA originate from V(D)J recombination or somatic hypermutation (SHM) is not known. We studied a mouse model of SLE in which all somatic mutations within ANA V regions, including those in CDR3, could be unequivocally identified. Mutation reversion analyses revealed that ANA arose predominantly from nonautoreactive B cells that diversified immunoglobulin genes via SHM. The resolution afforded by this model allowed us to demonstrate that one ANA clone was generated by SHM after a VH gene replacement event. Mutations producing arginine substitutions were frequent and arose largely (66%) from base changes in just two codons: AGC and AGT. These codons are abundant in the repertoires of mouse and human V genes. Our findings reveal the predominant role of SHM in the development of ANA and underscore the importance of self-tolerance checkpoints at the postmutational stage of B cell differentiation