CDK inhibitor p18(INK4c) is required for the generation of functional plasma cells

Immunity. 2002 Aug;17(2):179-89. doi: 10.1016/s1074-7613(02)00364-3.

Abstract

B cell terminal differentiation is associated with the onset of high-level antibody secretion and cell cycle arrest. Here the cyclin-dependent kinase (CDK) inhibitor p18(INK4c) is shown to be required within B cells for both terminating cell proliferation and differentiation of functional plasma cells. In its absence, B cells hyperproliferate in germinal centers and extrafollicular foci in response to T-dependent antigens but serum antibody titers are severely reduced, despite unimpaired germinal center formation, class switch recombination, variable region-directed hypermutation, and differentiation to antibody-containing plasmacytoid cells. The novel link between cell cycle control and plasma cell differentiation may, at least in part, relate to p18(INK4c) inhibition of CDK6. Cell cycle arrest mediated by p18(INK4C) is therefore requisite for the generation of functional plasma cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Formation
  • Apoptosis
  • CD40 Antigens / immunology
  • Cell Cycle
  • Cell Cycle Proteins*
  • Cell Differentiation
  • Cell Division
  • Cyclin-Dependent Kinase 6
  • Cyclin-Dependent Kinase Inhibitor p18
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Enzyme Inhibitors / immunology*
  • Germinal Center
  • Mice
  • Mice, Knockout
  • Plasma Cells / cytology*
  • Plasma Cells / immunology
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Signal Transduction / immunology
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / immunology*

Substances

  • CD40 Antigens
  • Cdkn2c protein, mouse
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p18
  • Enzyme Inhibitors
  • Tumor Suppressor Proteins
  • Protein-Serine-Threonine Kinases
  • Cdk6 protein, mouse
  • Cyclin-Dependent Kinase 6
  • Cyclin-Dependent Kinases