Thursday Seminar: Jonathan Visentin

Presentation entitled: “The DNA-sensor AIM2 Promotes BCR-activated B cells in Chronic Graft-versus-Host-Disease” Abstract: “Chronic graft-versus-host-disease (cGVHD) remains a common cause of late non-relapse morbidity/mortality after allogeneic hematopoietic stem cell transplantation (allo-HCT). T cells and IgG-producing B cells mediate cGVHD development and perpetuation. Molecular mechanisms driving cGVHD pathology require further study to develop new drugs. In this work, we are studying the function of AIM2 in B cells, as AIM2 is increased in activated B cells in cGVHD (Poe, bioRxiv 2022). AIM2 senses double-stranded DNA (dsDNA) to incite inflammasome-mediated pyroptosis in macrophages, but AIM2 function in B cells is largely unknown. Our results obtained with human B cells and mouse models of hapten-carrier immunization suggest that AIM2 has a non canonical function in B cells. Instead of inducing pyroptosis after DNA-sensing in the cytosol, AIM2 appears to be a transcriptional regulator located in the nucleus which modulates the germinal center reaction and antibody production. In mouse cGVHD, AIM2 could promote pathologic BCR-activated B cells. Thus, AIM2 may play a novel non-canonical inflammasome-independent role in cGVHD B cell pathology. We are actively investigating how AIM2 effects alloantibody production and cGVHD development, so that therapeutic targets can be identified.”