title: TNF signals are dispensable for the generation of CD23+ CD21/35-high CD1d-high B cells in inflamed lymph nodes.
abstract: Tumor necrosis factor (TNF) is a key cytokine in rheumatoid arthritis (RA) pathogenesis, as underscored by the clinical effectiveness of TNF antagonists. While several of TNF's key targets in RA are well understood, its many pleiotropic effects remain to be elucidated. TNF-transgenic mice develop inflammatory-erosive arthritis associated with disruption of draining lymph node histology and function, and accumulation of B cells with unique phenotypic and functional features consistent with contribution to pathogenesis (B cells in inflamed nodes, Bin). Bin cell induction depends on the inflamed microenvironment, but the specific signals are unknown. Using anti-TNF treatment and TNF-receptor-deficient mice, here we show that Bin cells are induced and maintained independently of B cell-intrinsic TNF signals.
authors.affiliation: Dept. of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA.
authors.forename: Igor I
authors.initials: II
authors.lastname: Kuzin
authors.affiliation: Center for Musculoskeletal Research, Dept. of Biomedical Engineering, and Dept. of Orthopaedics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Echoe M
authors.initials: EM
authors.lastname: Bouta
authors.affiliation: Center for Musculoskeletal Research, Dept. of Biomedical Engineering, and Dept. of Orthopaedics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.affiliation: Dept. of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: bottaro@rowan.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bottaro
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D060833:Cellular Microenvironment / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017463:Receptors, Complement 3b / Q000235:genetics / Q000276:immunology; D017464:Receptors, Complement 3d / Q000235:genetics / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology
chemical_list: D000906:Antibodies; D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha
keywords: B cells; Inflammation; Lymph nodes; Tumor necrosis factor