Cell-cycle control of plasma cell differentiation and tumorigenesis.
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.
Chen-Kiang
Selina
S
Department of Pathology, Weill Medical College of Cornell University, New York, NY 10021, USA. sckiang@med.cornell.edu
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism