ABSTRACT Support is requested for a Keystone Symposia conference entitled B Cell Biology in the Context of Infectious Diseases, Autoimmunity and B Cell Cancers, organized by Drs. Susan Pierce and Facundo Batista. The conference will be held in Keystone, Colorado from June 6 - 10, 2023. Effective B cell antibody responses are essential for human health and protection against deadly infectious diseases. However, B cell antibodies are also mediators of devastating autoimmune diseases, and, when released from normal control mechanisms, B cell malignancies are common; and many remain untreatable. It is also becoming evident that the mature B cell compartment is highly heterogeneous and that antigen-driven fates of individual B cells are dependent on several factors, including the affinity of the B cell receptor (BCR) and how the BCR is wired to the B cell’s activation machinery, along with the quality of the immune environment as defined by both antigen-specific T cells and innate immune cells responding to pathogen- derived signals. The generation of long-lived protective immunity versus B cell malignancies, or systemic autoimmunity, may represent the spectrum of outcomes resulting from variations in and interactions between these intrinsic factors and the surrounding context. If so, our ability to rationally manipulate B cell responses to develop vaccines against infectious diseases, as well as therapies for autoimmune diseases and B cell cancers, may be greatly accelerated by a detailed understanding of the fundamentals of B cell biology. The translation of this knowledge to clinical and basic research will allow the field to address the most pressing public health priorities of our times, ranging from acute and chronic infectious diseases to autoimmunity and B cell malignancies. Finally, this conference is being held jointly with the Keystone Symposia conference, HIV Vaccines, Immunoprophylaxis and Drugs. This pairing is ideal to discuss how B cell abnormalities contribute to HIV infection, especially in terms of the potential for antibody-based vaccine development. Participants from both conferences will have the opportunity to network through shared sessions, mealtimes, and evening poster sessions.