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

TitleCDK inhibitor p18(INK4c) is required for the generation of functional plasma cells.
Publication TypeJournal Article
Year of Publication2002
AuthorsTourigny MR, Ursini-Siegel J, Lee H, Toellner K-M, Cunningham AF, Franklin DS, Ely S, Chen M, Qin X-F, Xiong Y, Maclennan ICM, Chen-Kiang S
JournalImmunity
Volume17
Issue2
Pagination179-89
Date Published2002 Aug
ISSN1074-7613
KeywordsAnimals, Antibody Formation, Apoptosis, CD40 Antigens, Cell Cycle, Cell Cycle Proteins, Cell Differentiation, Cell Division, Cyclin-Dependent Kinase 6, Cyclin-Dependent Kinase Inhibitor p18, Cyclin-Dependent Kinases, Enzyme Inhibitors, Germinal Center, Mice, Mice, Knockout, Plasma Cells, Protein-Serine-Threonine Kinases, Signal Transduction, Tumor Suppressor Proteins
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.

DOI10.1016/s1074-7613(02)00364-3
Alternate JournalImmunity
PubMed ID12196289
Grant ListCA80204 / CA / NCI NIH HHS / United States
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