Decoding the B cell endotype in early onset T1D

Recent studies indicate the existence of two forms of type 1 diabetes distinguished by the age of onset. Importantly, one of the major defining characteristics between the two forms of disease is the presence of increased numbers of B cells in early onset T1D (<7 years) compared to late onset (>13 years). The increased numbers of B cells is associated with, and can even predict, rapid progression of disease as evidence by increased loss of C-peptide. Despite the compelling evidence for a role of B cells in an aggressive form of T1D, it remains unknown which B cell subset(s) is the pathogenic offender, as well as its phenotype, activation, and functional status. This application seeks to address this deficit in our knowledge by comparing the B cell compartment in early onset to late onset and healthy controls using the most comprehensive B cell panel (>35 markers) used to date and high-dimensional mass cytometry (CyTOF). The significance of this proposal is that it aims to improve human health by developing fundamental knowledge in our understanding of the molecular mechanism of B cell involvement in rapid rate of progression, which may translate into future novel therapeutic targets to treat disease.