Antigen presentation by B cells guides programming of memory CD4 T cell responses to a TLR4-agonist containing vaccine

The contribution of B cells to immunity against many infectious diseases is unquestionably important and well characterized. Here we sought to determine the role of B cells in the induction of T helper 1 (T H 1) CD4+ T cells upon vaccination with a TB antigen combined with a TLR4 agonist. We used B cell deficient mice (μMT-/-), tetramer-positive CD4+ T cells, markers of memory ‘precursor’ effector cells (MPEC), and T cell adoptive transfers and demonstrated that the early antigen-specific cytokine-producing T H 1 responses are unaffected in the absence of B cells, however MPEC induction is strongly impaired resulting in a deficiency of the memory T H 1 response in μMT-/- mice. We further show that antigen-presentation by B cells was necessary for their role in MPEC generation using B cell adoptive transfers from wild type or MHC class II knock-out mice into μMT-/- mice. Our study challenges the view that B cell deficiency exclusively alters the T H 1 response at memory time-points. Collectively, our results provide new insightson the multifaceted roles of B cells which will have a high impact on vaccine development against several pathogens including those requiring T H 1 cell-mediated immunity.