Induction of cell cycle arrest and B cell terminal differentiation by CDK inhibitor p18(INK4c) and IL-6. Academic Article uri icon

Overview

abstract

  • Cell cycle arrest and cell death are tightly coupled to terminal differentiation of B cells to plasma cells in vivo. This process was recapitulated in vitro by stimulation of IgG-bearing human B lymphoblastoid cells with interleukin-6 (IL-6), which led to orderly cell cycle arrest, differentiation, and apoptosis. In terminally differentiated plasmacytoid cells, phosphorylation of pRb was suppressed, correlating with the activation of the D-type cyclin-dependent kinase (CDK) inhibitors p18(INK4c) and p21(WAF1/CIP1). The expression of CDK6, however, remained unchanged. Activation of p18 by IL-6 was rapid, concomitant with marked enhancement of its association with CDK6 and cell cycle arrest. Overexpression of p18 in IgM-bearing lymphoblastoid cells, which differentiated in response to IL-6 but did not exit the cell cycle, reconstituted coupled differentiation and cell cycle arrest. Thus, CDK inhibitors, in particular p18, are likely to play a pivotal role in controlling cell cycle arrest and cell death in terminal differentiation of late-stage B cells to plasma cells via inhibition of pRb phosphorylation by CDK6.

publication date

  • January 1, 1997

Research

keywords

  • B-Lymphocytes
  • Carrier Proteins
  • Cell Cycle
  • Cell Cycle Proteins
  • Cell Differentiation
  • Cyclin-Dependent Kinases
  • Enzyme Inhibitors
  • Interleukin-6
  • Plasma Cells
  • Tumor Suppressor Proteins

Identity

Scopus Document Identifier

  • 0030891628

Digital Object Identifier (DOI)

  • 10.1016/s1074-7613(00)80241-1

PubMed ID

  • 9052836

Additional Document Info

volume

  • 6

issue

  • 1