title: IL-17A Promotes Pulmonary B-1a Cell Differentiation via Induction of Blimp-1 Expression during Influenza Virus Infection.
abstract: B-1 cells play a critical role in early protection during influenza infections by producing natural IgM antibodies. However, the underlying mechanisms involved in regulating this process are largely unknown. Here we found that during influenza infection pleural cavity B-1a cells rapidly infiltrated lungs, where they underwent plasmacytic differentiation with enhanced IgM production. This process was promoted by IL-17A signaling via induction of Blimp-1 expression and NF-κB activation in B-1a cells. Deficiency of IL-17A led to severely impaired B-1a-derived antibody production in the respiratory tract, resulting in a deficiency in viral clearance. Transfer of B-1a-derived natural antibodies rescued Il17a-/- mice from otherwise lethal infections. Together, we identify a critical function of IL-17A in promoting the plasmacytic differentiation of B-1a cells. Our findings provide new insights into the mechanisms underlying the regulation of pulmonary B-1a cell response against influenza infection.
authors.affiliation: Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
authors.forename: Kongyang
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
authors.forename: King-Hung
authors.initials: KH
authors.lastname: Ko
authors.affiliation: Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
authors.forename: Bo-Jian
authors.initials: BJ
authors.lastname: Zheng
authors.affiliation: Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D047369:Chromatin Immunoprecipitation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D020381:Interleukin-17 / Q000172:deficiency / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D060888:Real-Time Polymerase Chain Reaction; D012141:Respiratory Tract Infections / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000276:immunology
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17; C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1