Abstract
Previously, we have documented that isolated autophagosomes from tumor cells could efficiently cross-prime tumor-reactive naïve T cells and mediate tumor regression in preclinical mouse models. However, the effect of tumor-derived autophagosomes, here we refer as to DRibbles, on B cells has not been studied so far. At present study, we found that DRibbles generated from a murine hepatoma cell line Hep1-6, induced B-cell activation after intravenous injection into mice. B-cell populations were significantly expanded and the production of Hep1-6 tumor-specific antibodies was successfully induced. Moreover, in vitro studies showed that DRibbles could induce more efficient B-cell proliferation and activation, antibody production, and cytokine secretion than whole tumor cell lysates. Notably, we found that B-cell activation required proteins but not DNA in the DRibbles. We further showed that B cells could capture DRibbles and present antigens in the DRibbles to directly induce T cell activation. Furthermore, we found that B-cell activation, antibody production, cytokine secretion and antigen cross-presentation were TLR2-MyD88 pathway dependent. Taken together, the present studies demonstrated that tumor-derived autophagosomes (DRibbles) efficiently induced B cells activation, antibody production, cytokine secretion and antigen cross-presentation mainly depending on their protein component via TLR2/MyD88 dependent manner.
Highlights
Autophagy is a cellular process in which portions of the cytoplasm are sequestered by double membrane vesicles termed autophagosomes [1]
To examine whether DRibbles could induce antibody production in vivo, C57/BL6 mice were injected intravenously with DRibbles derived from a murine hepatoma cell line (Hep 1-6) and serum samples were collected at day 7 after first injection of DRibbles
When antigens bear repeating determinants expressed at high density they can activate specific B cells for further differentiation and antibody production in a T-independent manner [19]
Summary
Autophagy is a cellular process in which portions of the cytoplasm are sequestered by double membrane vesicles termed autophagosomes [1]. With induction of autophagy and inhibition of lysosomal/proteasome activity, a broad spectrum of cellular antigens, including long-lived proteins, short-lived proteins, and defective ribosomal products (DRiPs), is sequestered in autophagosomes. Recent studies show that B cells express most Toll like receptors (TLRs) and can respond to a variety of TLR ligands [8,9]. Following these stimuli, B cells can proliferate and differentiate into antibody secreting cells, becoming more efficient antigen-presenting cells or cytokine producer cells [10]. It is highly desirable for vaccine to be able to induce strong B cell and
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