Some T cell subsets, such as Tfh and iNKT cells, have been shown to provide help for B cell activation, differentiation and antibody production. However, the role of MAIT cells in promoting similar effects has not been examined, despite clinical evidence showing an association of MAIT cell frequencies with increases in LPS-specific antibody responses in cholera patients and shigella vaccinees. In this study, we investigate the effect of coculturing primary human B cells with MAIT cells in vitro. Several different cytokines known to activate MAIT cells, such as interleukin (IL)-7, IL-12, IL-15, and IL-18, were tested for their ability to promote MAIT cell activation and MAIT-mediated activation of primary B cells. Paraformaldehyde-fixed E coli were tested alone or in combination with cytokines in cocultures. We have found that the specific combination of IL-12 and IL-15 was sufficient in cocultures of MAIT and B cells, but not B cells alone, to induce high levels of IgM, IgG, and IgA antibody. In addition to increased antibody levels in culture supernatants, IL-12 and IL-15 in cocultures led to significantly higher levels of IgD^- CD27⁺ isotype switched memory B cells. Addition of fixed E coli along with IL-12 and IL-15 led to increased antibody levels compared to cytokines alone. Finally, we also generated monoclonal populations of MAIT cells isolated by single cell sorting, and found that monoclonally derived MAIT cells were also capable of inducing higher levels of antibody production. This study thus provides the first direct evidence of a new role of MAIT cells, that of promoting B cell differentiation and antibody production.