Antigen presentation by B cells guides programing of memory CD4+ T-cell responses to a TLR4-agonist containing vaccine in mice

Abstract

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 tuberculosis (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 (MPECs), 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 is necessary for their role in MPEC generation using B-cell adoptive transfers from wt 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 insights on the multifaceted roles of B cells that will have a high impact on vaccine development against several pathogens including those requiring T_H 1 cell-mediated immunity.

Keywords: B cells · T cells · μMT−/− mice · memory precursor effector cells · TLR4 agonist.