title: Regulation of B cell differentiation by the ubiquitin-binding protein TAX1BP1.
abstract: Tax1-binding protein 1 (TAX1BP1) is a ubiquitin-binding protein that restricts nuclear factor-κB (NF-κB) activation and facilitates the termination of aberrant inflammation. However, its roles in B-cell activation and differentiation are poorly understood. To evaluate the function of TAX1BP1 in B cells, we established TAX1BP1-deficient DT40 B cells that are hyper-responsive to CD40-induced extracellular signal-regulated kinase (ERK) activation signaling, exhibit prolonged and exaggerated ERK phosphorylation and show enhanced B lymphocyte-induced maturation protein 1 (Blimp-1; a transcription factor inducing plasma cell differentiation) expression that is ERK-dependent. Furthermore, TAX1BP1-deficient cells exhibit significantly decreased surface IgM expression and increased IgM secretion. Moreover, TAX1BP1-deficient mice display reduced germinal center formation and antigen-specific antibody production. These findings show that TAX1BP1 restricts ERK activation and Blimp-1 expression and regulates germinal center formation.
authors: Laboratory of Molecular Biochemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors: Nobuko
authors: N
authors: Matsushita
authors: Laboratory of Molecular Biochemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors: Midori
authors: M
authors: Suzuki
authors: Department of Microbiology, Oita University Faculty of Medicine, Yufu, Oita, 879-5593, Japan.
authors: Emi
authors: E
authors: Ikebe
authors: Laboratory of Molecular Biochemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors: Shun
authors: S
authors: Nagashima
authors: Laboratory of Molecular Biochemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors: Ryoko
authors: R
authors: Inatome
authors: Laboratory of Immune Regulation, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors: Kenichi
authors: K
authors: Asano
authors: Laboratory of Immune Regulation, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors: Masato
authors: M
authors: Tanaka
authors: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan.
authors: Masayuki
authors: M
authors: Matsushita
authors: Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
authors: Eisaku
authors: E
authors: Kondo
authors: Department of Microbiology, Oita University Faculty of Medicine, Yufu, Oita, 879-5593, Japan.
authors: Hidekatsu
authors: H
authors: Iha
authors: Laboratory of Molecular Biochemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors: Shigeru
authors: S
authors: Yanagi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002645:Chickens; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1 / Q000235:genetics / Q000276:immunology
chemical_list: D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C513258:Prdm1 protein, mouse; C523855:TAX1BP1 protein, mouse; D000074462:Positive Regulatory Domain I-Binding Factor 1; D048049:Extracellular Signal-Regulated MAP Kinases