Thus, we speculate that the T-bethi B cells, which are found in HD and autoimmune patients in the settings of acute and chronic inflammation driven by vaccination, infection, autoimmunity and aging, are formed in an IFNγ-dependent manner and likely represent a pool of primary and secondary pre-ASCs as well as effector memory B cells that are epigenetically poised to differentiate. The gene discussed is IFNG; the disease is infection.