Inhibition of human B lymphocyte cell cycle progression and differentiation by rapamycin

Cellular Immunology
K M Aagaard-Tillery, D F Jelinek

Abstract

In this study, we have analyzed the effects of the immunosuppressive agent rapamycin on the activation of highly purified normal human B lymphocytes. When the polyclonal activators Staphylococcus aureus (SA) and soluble CD40 ligand (CD40L) were used to stimulate B cells, rapamycin inhibited both interleukin 2 (IL2)-dependent and -independent proliferation, as well as IL2-dependent differentiation into antibody-secreting cells. Cell cycle analysis indicated that rapamycin inhibited the progression of SA+IL2-stimulated B cells past the mid-G1 phase of the cell cycle. To begin to identify rapamycin-sensitive signaling events essential for B cell activation, we examined the effects of rapamycin on p34cdc2 and p33cdk2 kinase activities. SA+IL2 stimulation induced the activation of both cyclin-dependent kinases. Of interest, rapamycin abrogated the activation of both p34cdc2 and p33cdk2. Our results indicate therefore that rapamycin inhibits a number of SA- and CD40L-inducible events that may be necessary for both entry into S phase and for permitting subsequent B cell differentiation. These studies emphasize the utility of this drug as a tool to begin to dissect the activation pathways utilized by human B cells, as well as to provid...Continue Reading

Citations

Jul 1, 2010·The Journal of Antibiotics·Sung Ryeol ParkYeo Joon Yoon
Apr 25, 2009·Nature Reviews. Immunology·Angus W ThomsonGiorgio Raimondi
Feb 22, 2008·The New England Journal of Medicine·Nassim KamarLionel Rostaing
Nov 21, 1995·Proceedings of the National Academy of Sciences of the United States of America·W C YehS L McKnight
Jun 1, 2005·The British Journal of Ophthalmology·V A ShanmuganathanH S Dua
Aug 29, 2007·International Journal of Nanomedicine·Li-Jiuan Shen, Fe-Lin Lin Wu
Aug 2, 2014·PloS One·Yingchi ZhangWeiping Yuan
Jan 30, 2014·International Reviews of Immunology·Tiffany CazaAndras Perl
Apr 28, 2007·Expert Opinion on Investigational Drugs·Jean-Pierre Venetz, Manuel Pascual
Jan 3, 2001·Kidney International·R N SaundersM L Nicholson
Jan 29, 2013·Seminars in Immunology·Xiaojin XuRafi Ahmed
Jun 18, 2010·Autoimmunity Reviews·Gabriele SimoniniRolando Cimaz
Nov 26, 2008·Transplantation Reviews·Neeraj SinghMillie Samaniego
Mar 26, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Kelan A HlavatyStephen D Miller
Jul 25, 2007·Journal of Biomedical Materials Research. Part a·Azita HaddadiJohn Samuel
Oct 17, 2008·European Journal of Immunology·Frank SchmitzHermann Wagner
Aug 29, 2007·European Journal of Immunology·Amber C Donahue, David A Fruman
May 12, 2006·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A MercalliL Piemonti
Feb 3, 2005·Transplantation Proceedings·Q-Y Liu, P Nambi
Feb 17, 2015·Clinical and Experimental Immunology·R De BruyneM Dullaers
Jun 21, 2006·Seminars in Fetal & Neonatal Medicine·Kjersti M Aagaard-TilleryJess Dalton
Sep 27, 2013·Clinical & Developmental Immunology·Stavros StratakisEugene Daphnis
Sep 2, 2004·Respiratory Medicine·David ShitritMordechai R Kramer
Apr 26, 2001·The Journal of Surgical Research·L W KraissN M Alto
Nov 12, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jose J LimonDavid A Fruman
Jun 1, 2016·Frontiers in Immunology·Rachael Keating, Maureen Ann McGargill
Mar 19, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·B OhJ Kwun
Sep 11, 2016·Journal of Industrial Microbiology & Biotechnology·Young Ji YooYeo Joon Yoon
Apr 8, 2009·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Stephan KoromWalter Weder
May 26, 2017·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Yusuke TakeshimaKazuhiko Yamamoto
Mar 14, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ariel L RaybuckMark R Boothby

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

B cell Activation

B cell activation is initiated by the ligation of the B cell receptor with antigen and ultimately results in the production of protective antibodies against potentially pathogenic invaders. Here is the latest research.

B cell Differentiation

Depending on the signal received through the B cell receptor and other receptors, B cells differentiate into follicular or marginal zone B cells. Here is the latest research pertaining to this differentiation process.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.