title: Arachidonate 5-lipoxygenase establishes adaptive humoral immunity by controlling primary B cells and their cognate T-cell help.
abstract: In this study, we report the unique role of arachidonate 5-lipoxygenase (Alox5) in the regulation of specific humoral immune responses. We previously reported an L22 monoclonal antibody with which human primary resting B cells in the mantle zones of lymphoid follicles are well-defined. Proteomics analyses enabled identification of an L22 antigen as Alox5, which was highly expressed by naive and memory B cells surrounding germinal centers. Cellular growth of mantle cell lymphoma cells also seemed to depend on Alox5. Alox5(-/-) mice exhibited weak antibody responses specific to foreign antigens at the initial and recall phases. This was probably attributable to the low number of follicular and memory B cells and the functional loss of interleukin-21-mediated responses of follicular B cells. Moreover, Alox5(-/-) mice could not fully foster the development of follicular B helper T (Tfh) cells even after immunization with foreign antigens. Further experiments indicated that Alox5 affected mortality in experimentally induced enterocolitis in germ-prone circumstances, indicating that Alox5 would endow immunologic milieu. Our results illustrate the novel role of Alox5 in adaptive humoral immunity by managing primary B cells and Tfh cells in vivo.
authors.affiliation: Department of Pathology Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nagashima
authors.forename: Shingo
authors.initials: S
authors.lastname: Ichimiya
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumiya
authors.forename: Shihoko
authors.initials: S
authors.lastname: Ara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Koshiba
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Chizuru
authors.initials: C
authors.lastname: Hatate
authors.forename: Akiko
authors.initials: A
authors.lastname: Tonooka
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kubo
authors.forename: Rui Carrie
authors.initials: RC
authors.lastname: Ye
authors.forename: Bungo
authors.initials: B
authors.lastname: Hirose
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shirasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Izumi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takami
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Himi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D004760:Enterocolitis / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics; D020522:Lymphoma, Mantle-Cell / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein; D001094:Arachidonate 5-Lipoxygenase