CD40-mediated induction of p21 accumulation in resting and cycling B cells.
The accumulation of G1 cell cycle-related proteins by resting or cycling B cells stimulated with B cell antigen receptor (BCR)- and T helper (Th) cell-derived signals is documented. Resting B cells constitutively express cyclin dependent kinase (cdk)4, cdk2 and the cyclin dependent kinase inhibitor (CKI), p27. The initiation of optimal proliferation with F(ab')2 anti-mu plus paraformaldehyde-fixed CD40 ligand-baculovirus-infected Sf9 cells (CD40L/Sf9 cells) increases accumulation of both cdk4 and cdk2 while decreasing p27 levels. B cells express cyclin D2 early during cycle progression, while cyclin D3 and E are not expressed until 18 h poststimulation and cyclin A by 24 h poststimulation. Cycling B cells express heightened levels of all these cyclins and cdks. Although neither BCR- nor CD40-mediated signals appreciably alter cycling B cell accumulation of cyclins D2, cdk4 and cdk2, the absence of BCR-derived signals results in a decreased accumulation of cyclins D3 and E. Finally, CD40-mediated signals induce resting B cells to accumulate the CKI, p21, while cycling B cells require both BCR- and CD40-mediated signals to maintain increased expression of p21. Thus, a Th cell-derived signal may impact upon both resting and cycling B cell cycle progression, at least in part, by regulating the accumulation of p21. The functional consequences of p21 accumulation as cells enter and move through the cell cycle are discussed.
Mullins
M W
MW
Department of Microbiology & Immunology, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Pittner
B T
BT
Snow
E C
EC
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D019013:CD40 Antigens / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000502:physiology*; D008211:Lymphocyte Cooperation; D051379:Mice; D008811:Mice, Inbred DBA; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D009124:Muscle Proteins; D011506:Proteins; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D025521:Tumor Suppressor Proteins
D019013:CD40 Antigens; C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D007476:Ionophores; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009124:Muscle Proteins; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; C058992:Tagln protein, mouse; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate