Technological advances have markedly improved our ability to quantify and understand human immune responses to vaccines and pathogens. Sampling peripheral blood is both informative and practical, and by far the most common source of human immunology data. However, several central processes that initiate and regulate adaptive immunity are restricted to lymphoid tissue sites, such as the lymph nodes, tonsils and spleen. Animal models provide a solid foundational understanding of these events, but pre-clinical studies continue to poorly predict the magnitude and quality of vaccine responses in humans. A better understanding of human lymphoid tissue biology and the inner workings of the responding cells during a productive adaptive immune response will be crucial to inform rational vaccine and adjuvant design. To work towards this goal, we developed an in vitro immune organoid system, derived from readily available primary human lymphoid tissues (tonsils), that recapitulates several essential features of the adaptive immune response.