Regulation of B cell differentiation by the ubiquitin-binding protein TAX1BP1

• Published in: Scientific reports 2016-08, Vol.6 (1), p.31266-31266, Article 31266
• Main Authors: Matsushita, Nobuko, Suzuki, Midori, Ikebe, Emi, Nagashima, Shun, Inatome, Ryoko, Asano, Kenichi, Tanaka, Masato, Matsushita, Masayuki, Kondo, Eisaku, Iha, Hidekatsu, Yanagi, Shigeru
• Format: Article
• Language: English
• Subjects: 631/250/516/1909; 631/80/458/1733; Animals; B-Lymphocytes - cytology; B-Lymphocytes - immunology; CD40 antigen; Cell activation; Cell differentiation; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Line; Chickens; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - immunology; Germinal Center - cytology; Germinal Center - immunology; Humanities and Social Sciences; Immunoglobulin M; Immunoglobulin M - genetics; Immunoglobulin M - immunology; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - immunology; Lymphocytes; Lymphocytes B; Male; Mice; Mice, Knockout; multidisciplinary; Neoplasm Proteins - genetics; Neoplasm Proteins - immunology; Phosphorylation; Positive Regulatory Domain I-Binding Factor 1 - genetics; Positive Regulatory Domain I-Binding Factor 1 - immunology; Proteins; Rodents; Science; Ubiquitin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep31266

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.