Antigen affinity and site of immunization dictate B cell recall responses

Protective antibodies against HIV-1 require unusually high levels of somatic mutations introduced in germinal centers (GCs). To achieve this, a sequential vaccination approach was proposed. Using HIV-1 antibody knockin mice with fate-mapping genes, we examined if antigen affinity affects the outcome of B cell recall responses. Compared to a high-affinity boost, a low-affinity boost resulted in decreased numbers of memory-derived B cells in secondary GCs but with higher average levels of somatic mutations, indicating an affinity threshold for memory B cells to enter GCs. Furthermore, upon boosting local lymph nodes (LNs), the composition of primary GCs was modified in an antigen-affinity-dependent manner to constitute less somatically mutated B cells. Our results demonstrate that antigen affinity and location of the boost affect the outcome of the B cell recall response. These results can help guide the design of vaccine immunogens aiming to selectively engage specific B cell clones for further diversification.