Cell-cycle control of plasma cell differentiation and tumorigenesis

Immunol Rev. 2003 Aug;194:39-47. doi: 10.1034/j.1600-065x.2003.00065.x.

Abstract

Cell-cycle control is a major determinant of homeostasis during B-cell development, differentiation, and tumorigenesis. The generation of an antibody response requires activation and expansion of antigen-specific B cells and terminal differentiation of these cells into plasma cells. Plasma cells arrest in the G1 phase of the cell cycle, but the mechanism that underlies timely cell-cycle entry and exit in the humoral immune response is not known. The mammalian cell-cycle is regulated primarily at the G1 to S transition by the balance between positive regulators, the cyclin-dependent kinases (CDK) together with cyclins, and negative regulators, the CDK inhibitors. One such inhibitor, p18INK4c, has been shown to be required for cell-cycle termination and final differentiation of non-secreting plasmacytoid cells to antibody-secreting plasma cells. This finding provides the first direct evidence for cell-cycle control of B-cell immunity. It also raises important questions regarding cell-cycle control of cellular differentiation, apoptosis, and earlier steps of B-cell terminal differentiation. This article discusses the biochemical mechanism of cell-cycle control in the context of antibody response and plasma cell differentiation along with the role of cell-cycle dysregulation in the pathogenesis of multiple myeloma, the plasma cell cancer.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle*
  • Cell Differentiation*
  • Cell Transformation, Neoplastic*
  • Humans
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology
  • Plasma Cells / cytology*
  • Plasma Cells / immunology*
  • Plasma Cells / metabolism