T-dependent activation of B cell proliferation is crucial to humoral immune responses. Regulation of this activation is required to limit responses. The cyclin dependent kinase (CDK) inhibitor (CKI) p21cip-1/waf-1 is implicated in inhibition of cell cycle progression. This thesis describes experiments that investigated the role of p21cip-1/waf-1 in regulating B cell proliferation. C57Bl/6 splenic B cells were stimulated to enter cell cycle by crosslinking CD40. p21cip-1/waf-1 expression was upregulated by CD40 stimulation of B cells, and superinduced by co-crosslinking intercellular adhesion molecule 1 (ICAM-1)/CD54, major histocompatibility complex (MHC) I or MHC II with CD40. Treatments that superinduced p21 cip-1/waf-1 inhibited CD40-stimulated proliferation and induced apoptosis. Apoptosis was abrogated in p21cip-1/waf-1-/- B cells, which otherwise responded equivalently to controls. By contrast, B cells from p27cip-1/waf-1-/- mice showed the same induction of cell death as wild type mice. These results show that MHC and ICAM-1, specifically modulate CD40-mediated signals and this process involves p21cip-1/waf-1.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.30370 |
| Date | January 1999 |
| Creators | Doyle, Iris S. |
| Contributors | Owens, Trevor (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Microbiology and Immunology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001740638, proquestno: MQ64346, Theses scanned by UMI/ProQuest. |
Page generated in 0.0019 seconds