Signaling and cell cycle regulation in B lymphocytes

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