Priming of naive lymphocytes is important for yielding efficient immune responses. Mechanisms controlling this process are also important for preventing immune cells from attacking self-antigens. It is well known that signals provided by innate immune receptors, such as Toll-like receptors (TLR), are essential to induce dendritic cell maturation that subsequently allows the priming of naive T cells. In this issue of the European Journal of Immunology, it is shown that TLR stimulation effectively potentiates naive human B cell activation and production of antibodies in T-dependent immune responses. TLR signals can be delivered to B cells directly, or indirectly via cytokines provided by TLR-activated dendritic cells.