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Updated: Oct 11, 2026

Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
The expression of p18INK4 and p27kip1 cyclin-dependent kinase inhibitors is regulated differently during human B cell
N Schrantz1, G E Beney, M T Auffredou
1Institut National de la Santé et de la Recherche Médicale, Unité 131, and Centre de Recherche Claude Bernard, Clamart, France.
Abstract:
Cell cycle progression is under the control of cyclin-dependent kinases (cdks), the activity of which is dependent on the expression of specific cdk inhibitors. In this paper we report that the two cdk inhibitors, p27(Kip1) and p18(INK4c), are differently expressed and control different steps of human B lymphocyte activation. Resting B cells contain large amounts of p27(Kip1) and no p18(INK4c). In vitro stimulation by Staphylococcus aureus Cowan 1 strain or CD40 ligand associated with IL-10 and IL-2 induces a rapid decrease in p27(Kip1) expression combined with cell cycle entry and progression. In contrast, in vitro Ig production correlates with specific expression of p18(INK4c) and early G(1) arrest. This G(1) arrest is associated with inhibition of cyclin D3/cdk6-mediated retinoblastoma protein phosphorylation by p18(INK4c). A similar contrasting pattern of p18(INK4c) and p27(Kip1) expression is observed both in B cells activated in vivo and in various leukemic cells. Expression of p18(INK4c) was also detected in various Ig-secreting cell lines in which both maximum Ig secretion and specific p18(INK4c) expression were observed during the G(1) phase. Our study shows that p27(Kip1) and p18(INK4c) have different roles in B cell activation; p27(Kip1) is involved in the control of cell cycle entry, and p18(INK4c) is involved in the subsequent early G(1) arrest necessary for terminal B lymphocyte differentiation.
Insights
Two cyclin-dependent kinase inhibitors, p27(Kip1) and p18(INK4c), regulate distinct stages of human B lymphocyte activation. p27(Kip1) controls cell cycle entry, while p18(INK4c) mediates early G(1) arrest for terminal differentiation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Cell cycle progression is regulated by cyclin-dependent kinases (cdks) and their inhibitors.
- Human B lymphocyte activation involves complex regulatory mechanisms controlling cell division and differentiation.
Purpose of the Study:
- To investigate the differential roles of p27(Kip1) and p18(INK4c) in human B lymphocyte activation.
- To elucidate the specific cell cycle phases controlled by these two cdk inhibitors.
Main Methods:
- Analysis of p27(Kip1) and p18(INK4c) expression in human B cells stimulated in vitro and in vivo.
- Assessment of cell cycle progression and immunoglobulin (Ig) production.
- Investigation of cyclin D3/cdk6-mediated retinoblastoma protein phosphorylation.
Main Results:
- Resting B cells express high p27(Kip1) and no p18(INK4c).
- In vitro stimulation decreases p27(Kip1), promoting cell cycle entry.
- Ig production correlates with p18(INK4c) expression and early G(1) arrest, inhibiting cyclin D3/cdk6 activity.
Conclusions:
- p27(Kip1) and p18(INK4c) play distinct roles in B lymphocyte activation.
- p27(Kip1) is crucial for initiating cell cycle entry.
- p18(INK4c) is essential for early G(1) arrest, facilitating terminal B lymphocyte differentiation.
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