B cells harbor polyclonal immune-checkpoint mutations in autoimmune thyroid disease

Using whole-exome sequencing and NanoSeq, researchers detected numerous B-cell clones with loss-of-function mutations in HVEM (TNFRSF14) and PD-L1 (CD274) in inflamed autoimmune thyroid tissue. In highly inflamed samples there are tens to hundreds of independent mutant clones, often with multiple hits and occasional biallelic loss, localizing to self-reactive B cells and supporting a model in which somatic immune-regulatory mutations contribute to thyroid autoimmunity.