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

Sci Rep. 2016 Aug 12;6:31266. doi: 10.1038/srep31266.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Line
  • Chickens
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / immunology
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Male
  • Mice
  • Mice, Knockout
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Positive Regulatory Domain I-Binding Factor 1 / genetics
  • Positive Regulatory Domain I-Binding Factor 1 / immunology

Substances

  • Immunoglobulin M
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Prdm1 protein, mouse
  • TAX1BP1 protein, mouse
  • Positive Regulatory Domain I-Binding Factor 1
  • Extracellular Signal-Regulated MAP Kinases