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Antibody responses are at the core of nearly every vaccine in clinical use today, yet our ability to rationally direct the antibody response remains limited. No strategies currently exist to selectively manipulate the antibody response. During an antibody response, T follicular helper CD4 cells (Tfh) provide critical help and direction to B cells. Over the past several years, we have developed approaches to look at Tfh in circulation and in tissue after vaccination. From these studies, we learned that circulating Tfh are a long-lived memory T cell population and can provide a "window" into the environment of the lymph node. We are interested in how Tfh repertoire is maintained, how the overall inflammatory environment shapes the T-B cell interaction, and how immunomodulatory therapeutics can be used to directly manipulate Tfh activity in research subjects. Understanding the T cells at the heart of a vaccine response will be crucial to designing personalized, rational vaccine strategies as well as myriad other scenarios where antibody responses are key.