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B cell-T cell interactions underlie the maturation and production of high-affinity antibodies, and are thus key to the establishment of effective humoral immunity. While this greatly enhances our ability to fight pathogens, it also can lead to the development of allergies and autoimmune disease. While recent years have seen a burst in our understanding of how B cell-T cell interactions drive antibody affinity maturation, a number of gaps remain, including how these interactions influence the differentiation of B cells into effector fates and how they limit the emergence of autoreactive B cell clones. Most importantly, from the vaccine standpoint, it is likely that better understanding of how T cells help shape the B cell repertoire will allow us to better control the specificity of vaccine-induced immune responses. The aim of this Keystone Symposia conference are to: 1) Present the most recent advances in the basic biology of the T cell-dependent B cell response, focusing on Tfh development and function and B cell activation and differentiation; 2) Address the gap in our understanding of the differentiation of B cells into post-activation (memory and plasma cell) fates; 3) Discuss how furthering our understanding of B-T cell interactions can inform vaccine development; and 4) Present recent findings regarding the role of T-dependent B cell response in allergy and autoimmunity.