ABSTRACT Support is requested for a Keystone Symposia conference entitled Humoral Immunity: From Regulation to Dysregulation, organized by Drs. Victor L.J. Tybulewicz, Kai-Michael Toellner, Julie Zikherman and Pamela Schwartzberg. The conference will be held in Hannover, Germany from April 3-6, 2022. Humoral immunity is at the heart of the adaptive immune response. The germinal center reaction orchestrates critical B cell-T cell collaboration, leading to the generation of B cell memory and long-lived affinity-matured protective antibodies. This key immune response has been extensively studied, and, as a result, there has been an increasingly refined understanding of the ligands, receptors, and intra-cellular pathways that are involved in this process. However, many aspects of this remarkable process, as it plays out in infections, vaccine responses, and chronic immunological diseases, remain unknown. For instance, there is no clear understanding on how B cells integrate complex antigenic and co-stimulatory inputs over time to make critical cell fate decisions, including the process of clonal selection in the germinal center as well as memory B cell and long-lived plasma cell differentiation. Additionally, there is not a full appreciation for the spectrum of ‘non- canonical’ B cell responses to various chronic and acute infections, especially those occurring in tissues rather than secondary lymphoid organs. And finally, many unanswered questions remain about normal and abnormal B cell responses to commensal flora, allergic antigens, and self-antigens that are essential to address if researchers hope to understand dysregulated B cell immune responses in inflammatory, allergic, and autoimmune diseases. Therefore, this conference brings together scientists focused on both the B cell and the Tfh cell contributions to humoral immunity in order to share innovative research focused on addressing this broad set of questions. It is a goal of this conference to identify areas of future investigation, foster collaboration, and collectively generate the knowledge base required to design better vaccines and more precise strategies to treat diseases of immune dysregulation.