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

TitleInduction of cell cycle arrest and B cell terminal differentiation by CDK inhibitor p18(INK4c) and IL-6.
Publication TypeJournal Article
Year of Publication1997
AuthorsMorse L, Chen D, Franklin D, Xiong Y, Chen-Kiang S
Date Published1997 Jan
KeywordsApoptosis, B-Lymphocytes, Carrier Proteins, Cell Cycle, Cell Cycle Proteins, Cell Differentiation, Cyclin-Dependent Kinase 6, Cyclin-Dependent Kinase Inhibitor p18, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases, Cyclins, Enzyme Inhibitors, HLA-D Antigens, Humans, Immunoglobulin G, Interleukin-6, Phosphorylation, Plasma Cells, Protein Binding, Protein-Serine-Threonine Kinases, Retinoblastoma Protein, Tumor Cells, Cultured, Tumor Suppressor Proteins

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.

Alternate JournalImmunity
PubMed ID9052836
Grant ListAR-24404 / AR / NIAMS NIH HHS / United States
CA-68377 / CA / NCI NIH HHS / United States
F32 AR08421 / AR / NIAMS NIH HHS / United States
Related Lab: 
Related Faculty: 
Selina Chen-Kiang, Ph.D.

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