title: 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 (TH1) 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 TH1 responses are unaffected in the absence of B cells, however MPEC induction is strongly impaired resulting in a deficiency of the memory TH1 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 TH1 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 TH1 cell-mediated immunity.
authors.affiliation: Infectious Disease Research Institute, Seattle, WA, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Dubois Cauwelaert
authors.affiliation: Infectious Disease Research Institute, Seattle, WA, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Baldwin
authors.affiliation: Infectious Disease Research Institute, Seattle, WA, USA.|Department of Global Health, University of Washington, Seattle, WA, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Orr
authors.affiliation: Infectious Disease Research Institute, Seattle, WA, USA.|Aduro Biotech, Berkeley, CA, USA.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Desbien
authors.affiliation: Infectious Disease Research Institute, Seattle, WA, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Gage
authors.affiliation: Infectious Disease Research Institute, Seattle, WA, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Hofmeyer
authors.affiliation: Infectious Disease Research Institute, Seattle, WA, USA.|Department of Global Health, University of Washington, Seattle, WA, USA.|PAI Life Sciences, Seattle, WA, USA.
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000502:physiology* / Q000637:transplantation; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007155:Immunologic Factors / Q000276:immunology*; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000819:agonists; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D007148:Immunoglobulin mu-Chains; D007155:Immunologic Factors; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D032581:Tuberculosis Vaccines
keywords: B cells · T cells · μMT−/− mice · memory precursor effector cells · TLR4 agonist