title: TRAF3IP3, a novel autophagy up-regulated gene, is involved in marginal zone B lymphocyte development and survival.
abstract: Tumour necrosis factor receptor-associated factor 3 (TRAF3) interacting protein 3 (TRAF3IP3; also known as T3JAM) is expressed specifically in immune organs and tissues. To investigate the impact of TRAF3IP3 on immunity, we generated Traf3ip3 knock-out (KO) mice. Interestingly, these mice exhibited a significant reduction in the number of common lymphoid progenitors (CLPs) and inhibition of B cell development in the bone marrow. Furthermore, Traf3ip3 KO mice lacked marginal zone (MZ) B cells in the spleen. Traf3ip3 KO mice also exhibited a reduced amount of serum natural antibodies and impaired T cell-independent type II (TI-II) responses to trinitrophenol (TNP)-Ficoll antigen. Additionally, our results showed that Traf3ip3 promotes autophagy via an ATG16L1-binding motif, and MZ B cells isolated from mutant mice showed a diminished level of autophagy and a high rate of apoptosis. These results suggest that TRAF3IP3 contributes to MZ B cell survival by up-regulating autophagy, thereby promoting the TI-II immune response.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.|Human Disease Genomics Center, Peking University, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.affiliation: Human Disease Genomics Center, Peking University, Beijing, China.|Department of Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.|Human Disease Genomics Center, Peking University, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Human Disease Genomics Center, Peking University, Beijing, China.|Department of Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Nan
authors.affiliation: Human Disease Genomics Center, Peking University, Beijing, China.|Department of Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Xing
authors.affiliation: Human Disease Genomics Center, Peking University, Beijing, China.|Department of Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Ge
authors.affiliation: Human Disease Genomics Center, Peking University, Beijing, China.|Department of Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001343:Autophagy / Q000235:genetics* / Q000276:immunology; D000071183:Autophagy-Related Proteins; D001402:B-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005362:Ficoll / Q000276:immunology; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D054503:Lymphoid Progenitor Cells / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology; D015854:Up-Regulation
chemical_list: C532820:Atg16l1 protein, mouse; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; C000602274:TRAF3IP3 protein, mouse; D014301:Trinitrobenzenes; D005362:Ficoll
keywords: Traf3ip3; apoptosis; autophagy; marginal zone B cell