B cells are critical to forming long-lived immunity, with plasma cells and memory B cells providing protection against reinfection. Yet, while so fundamental to human health and longevity, dysfunction of B cells during chronic infection, autoimmunity and lymphomas can drive immunopathogenesis and disease. This conference will explore recent advances in understanding core determinants of the longevity and effectiveness of humoral responses. It will detail how these advances can be used to specifically target B cells for therapeutic intervention and utilize antibodies for diagnostics and immunotherapies. Understanding these mechanisms has become even more timely, given the focus on newly emerging pathogens and their variants, the expanding portfolio of new vaccine platforms, and determining how to therapeutically engineer the B cell response. Our meeting brings together global experts in the fundamental and translational biology of plasma cells and memory B cells. We have designed the program to encompass ‘the instruction manual’ of building effective B cell responses. The program incorporates interdisciplinary talks on B cell repertoires in vaccine design, molecular mechanisms of promoting humoral memory longevity, understanding how ineffective and/or immunopathogenic antibody is produced, and new therapeutic strategies to ameliorate disease.