Cell-cycle control of plasma cell differentiation and tumorigenesis.

TitleCell-cycle control of plasma cell differentiation and tumorigenesis.
Publication TypeJournal Article
Year of Publication2003
AuthorsChen-Kiang S
JournalImmunol Rev
Volume194
Pagination39-47
Date Published2003 Aug
ISSN0105-2896
KeywordsAnimals, Cell Cycle, Cell Differentiation, Cell Transformation, Neoplastic, Humans, Multiple Myeloma, Plasma Cells
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.

DOI10.1034/j.1600-065x.2003.00065.x
Alternate JournalImmunol Rev
PubMed ID12846806
Grant ListAR 49436 / AR / NIAMS NIH HHS / United States
CA 80204 / CA / NCI NIH HHS / United States
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Selina Chen-Kiang, Ph.D.

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