title: Macrophages enhance tumor-derived autophagosomes (DRibbles)-induced B cells activation by TLR4/MyD88 and CD40/CD40L.
abstract: Our previous studies have showed that tumor-derived autophagosomes (termed "DRibbles") induce B cell activation, resulting in antibody production and cytokine secretion. Unexpectedly, we found that unfractionated splenocytes produced a higher level of antibody and cytokine than that of purified B cells. In the current study, we investigated the role of accessory cells in DRibbles-induced B cell activation. We found that cognate macrophages, but not T cells, significantly enhanced the B cell activities. Such an enhancement required cell-cell contact. Furthermore, DRibbles stimulation up-regulated CD40L expression on macrophages, resulting in increased level of CD40 expressed on B cells. The accessory role of macrophages in DRibbles-activated B cells is critically dependent on the CD40/CD40L interaction. In addition, the effects of macrophages were found to be largely dependent on TLR4 and MyD88 signaling pathway. Finally, our results showed that macrophages were able to enhance the antigen presentation function of B cells for specific T cell stimulation. Thus, these results suggest that macrophages play an important accessory role for DRibbles-induced B cell immune function.
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Weixia
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Zhifa
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Yemeng
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu Province, People׳s Republic of China; Cancer Research and Biotherapy Center, the Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Cao
authors.affiliation: Cancer Research and Biotherapy Center, the Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu Province, People׳s Republic of China; Laboratory of Cancer Immunobiology, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA. Electronic address: hhu@providence.org.
authors.forename: Hong-Ming
authors.initials: HM
authors.lastname: Hu
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu Province, People׳s Republic of China; Cancer Research and Biotherapy Center, the Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu Province, People׳s Republic of China. Electronic address: lxwang@seu.edu.cn.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Wang
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001343:Autophagy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D010588:Phagosomes / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D023201:CD40 Ligand
keywords: B cells; CD40/CD40L; Co-stimulation; Macrophages; TLRs; Tumor-derived autophagosomes (DRibbles)