Essential role of antigen-presenting cell-derived BAFF for antibody responses

Antigen-presenting cells (APC) are directly involved in survival, growth and differentiation of naive B cells and in immunoglobulin class switch recombination. Less is known about the contribution of APC to memory B cell responses. We employed an in vitro model to investigate the secondary humoral response against foot-and-mouth disease virus, with cells from a natural host of the virus - the pig. This response is T cell-dependent. Under conditions of limited T cell help, defined as a low T-to-B cell ratio or by the replacement of T cells with interleukin-2 only, the antibody response was dependent on APC. These included monocytes and monocyte-derived DC, but not plasmacytoid DC. APC mediated their help through soluble factors, particularly soluble B cell-activating factor belonging to the TNF family (BAFF). Our results suggest that the 'ménage à trois' concept, saying that both APC and T cells have a direct effect in B cell activation, is also valid for secondary B cell responses, and imply an important role for BAFF under conditions that might be physiologically relevant in secondary lymphoid organs.