B Cells Capturing Antigen Conjugated with CpG Oligodeoxynucleotides Induce Th1 Cells by Elaborating IL-12

Abstract

APCs initiate T cell-mediated immune responses against foreign Ags. Dendritic cells are professional APCs that play unique roles, including Ag-nonspecific capture, priming of naive T cells, and Th1 induction, whereas B cells generally lack these functions. In this study we uncovered novel aspects of murine B cells as APCs using CpG oligodeoxynucleotides (CpG) conjugated with an Ag. B cells served as efficient APCs independently of surface Igs. This characteristic was underlaid by the CpG-mediated Ag uptake and presentation, which were functional only when CpG were covalently conjugated to Ag. The B cells cultured with CpG-conjugated Ag not only enhanced IFN-γ formation by Th1 cells, but also induced Th1 differentiation from unprimed T cells. These effects paralleled with the increase in the expression of CD40, CD86, and class II molecules on B cells and the coordinated production of IL-12 by the cells. To our knowledge this is the first report revealing that B cells share with dendritic cells common intrinsic characteristics, such as the Ag-nonspecific capture and presentation, and the induction of Th1 differentiation from unprimed T cells.

Activated B cells modified by electroporation of multiple mRNAs encoding immune stimulatory molecules are comparable to mature dendritic cells in inducing in vitro antigen‐specific T‐cell responses

“…26 It has been shown that activated B cells produce IL-10 as well as IL-12p70, even under specific activation conditions. 3,7,19,27,28 In Fig. 3, B cells treated with CpG or LPS but not anti-CD40 produced IL-10 and IL-6 while LPS-matured DCs produced no IL-10 but did produce significantly greater amounts of IL-6 than activated B cells (P < 0Á05).…”

“…[1][2][3][4][5][6][7][8][9] In spite of their practical advantages over DCs, including their abundance in peripheral blood, ease of expansion, simple preparation and homogeneity, activated B cells have been shown to be less efficient stimulators of T cells than DCs. Croft et al 10 demonstrated that DCs were far superior to activated B cells in inducing proliferation and interleukin-2 (IL-2) production by naïve CD4 + T cells.…”

Marginal Zone, but Not Follicular B Cells, Are Potent Activators of Naive CD4 T Cells

“…Numerous studies both in vitro and in vivo suggest that B cells are involved in Th2 responses (68 -70). However, B cells activated with oligodeoxynucleotide (CpG)-conjugated Ag promote Th1 differentiation from unprimed T cells (71). Effector B cell subsets that produce distinct sets of cytokines, named Be1 and Be2, have been demonstrated to facilitate Th1 and Th2 polarization, respectively (72).…”

Potential of Transfected Muscle Cells to Contribute to DNA Vaccine Immunogenicity

“…After 1 day of culture, cells were fixed with 0.5% paraformaldehyde for 15 min at 37°C (22). After extensive washing, cells (2 ϫ 10 5 cells/well) were cocultured with 3 ϫ 10 4 OT-1 cells in 96-well plates.…”