Pamela L. Schwartzberg, MD, PhD, chief of the Cell Signaling and Immunity Section of the National Institutes of Health, discusses genetics and primary immunodeficiencies. Outcomes of T-cell activation include changes in transcription, metabolic changes, cytoskeletal changes, which contribute to clonal expansion. Dr Schwartzberg discusses research related to patients with heterozygous Pik3cd gain of function mutations, with a focus on follicular T helper cells.