CDK inhibitor p18(INK4c) is required for the generation of functional plasma cells.
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.
Department of Pathology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Michelle R
MR
Tourigny
Josie
J
Ursini-Siegel
Hayyoung
H
Lee
Kai-Michael
KM
Toellner
Adam F
AF
Cunningham
David S
DS
Franklin
Scott
S
Ely
Meihong
M
Chen
Xiao-Feng
XF
Qin
Yue
Y
Xiong
Ian C M
IC
MacLennan
Selina
S
Chen-Kiang
D000818:Animals; D000917:Antibody Formation; D017209:Apoptosis; D019013:CD40 Antigens / Q000276:immunology; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002455:Cell Division; D051361:Cyclin-Dependent Kinase 6; D050763:Cyclin-Dependent Kinase Inhibitor p18; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000276:immunology*; D018858:Germinal Center; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000276:immunology*
D019013:CD40 Antigens; C493972:Cdkn2c protein, mouse; D018797:Cell Cycle Proteins; D050763:Cyclin-Dependent Kinase Inhibitor p18; D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins; D017346:Protein Serine-Threonine Kinases; C495912:Cdk6 protein, mouse; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases