Mechanisms of dysfunctional T cell help in autoantibody disease are applicable to other forms of GC dysfunction. (A) Molecular mimicry is an etiology of MS and might be driven by the cross reactivity of the TFH repertoire. (B) In contrast, epitope spreading might enhance anti-tumor immune responses, although might also exacerbate irAE following immune checkpoint blockade in cancer. (C) T cell independent neutralizing antibodies against SARS-CoV-2 are made in COVID-19, although EF and pathogenic autoantibodies are also observed in severe COVID-19. GC, germinal center; TFH, follicular helper T cell; EBV, Epstein-Barr virus; MS, multiple sclerosis; irAE, immune related adverse event; EF, extrafollicular foci; MIS-C, multisystem inflammatory syndrome in children; PASC, post-acute sequelae of COVID-19.