Girelli Zubani et al. show that the Pms2 component of the mismatch repair complex and multiple uracil glycosylases contribute, each with a distinct strand bias, to enlarge the Ig gene mutation spectrum from G-C to A-T bases.

Highlights d Chronic viral infection elicits potent and sustained germinal center (GC) responses d Chronic infection triggers prolonged plasma cell and memory B cell output from GCs d GC B cells hypermutate efficiently and are potently selected in chronic infection