title: Tumor-derived autophagosomes (DRibbles) induce B cell activation in a TLR2-MyD88 dependent manner.
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.
authors: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu Province, People's Republic of China.
authors: Weixia
authors: W
authors: Li
authors: Meng
authors: M
authors: Zhou
authors: Hongyan
authors: H
authors: Ren
authors: Hong-Ming
authors: HM
authors: Hu
authors: Liwei
authors: L
authors: Lu
authors: Meng
authors: M
authors: Cao
authors: Li-xin
authors: LX
authors: Wang
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D001343:Autophagy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D010588:Phagosomes / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4