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B cell-T cell collaboration leads, via the germinal center reaction, 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, we have an increasingly refined understanding of the ligands, receptors, and intra-cellular pathways that are involved. However, many aspects of this remarkable process as it plays out in infections, vaccine responses, and chronic immunological diseases remain unknown. In particular, we still do not understand 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. We do not fully appreciate 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 we hope to understand dysregulated B cell immune responses in inflammatory, allergic, and autoimmune disease. This meeting 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. We aim 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.