Clast5/Stra13 is a negative regulator of B lymphocyte activation

Biochem Biophys Res Commun. 2002 Mar 22;292(1):121-7. doi: 10.1006/bbrc.2002.6605.

Abstract

CD40 is a member of the tumor necrosis factor receptor family and mediates a variety of functions of B cells, including B cell survival, proliferation, immunoglobulin gene class switching, memory B cell formation, and regulation of Fas-mediated apoptosis. To begin to elucidate the molecular mechanism governing such diverse functions of CD40, we have isolated a gene from mouse splenic B cells, termed Clast5, whose expression is strongly repressed during B cell activation. Clast5 is identical with Stra13, a recently identified member of the basic helix-loop-helix family of transcription factors. Clast5/Stra13 is highly expressed in unstimulated, resting B cells and is rapidly downregulated by a variety of stimuli that activate B cells, including CD40 ligand, anti-IgM antibodies, lipopolysaccharides and interleukin-4. Forced expression of Clast5/Stra13 in B cells delayed the cell cycle progression into S phase and strongly suppressed Fas-mediated apoptosis. Moreover, Clast5/Stra13 inhibited the colony formation in fibroblasts. Our results suggest that Clast5/Stra13 functions as a negative regulator of B cell activation by inhibiting cell cycle progression and cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Apoptosis
  • B-Lymphocytes / immunology*
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle
  • Cell Division
  • Cell Nucleus / chemistry
  • Cells, Cultured
  • Down-Regulation
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Immunoglobulin M / immunology
  • Kinetics
  • Lymphocyte Activation*
  • Lymphoma, B-Cell / metabolism
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / biosynthesis
  • Transfection
  • Tumor Cells, Cultured
  • fas Receptor / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Bhlhe40 protein, mouse
  • Homeodomain Proteins
  • Immunoglobulin M
  • RNA, Messenger
  • fas Receptor