Kurzfassung

B-lymphocytes participate in immune responses that require their proliferation, differen- tiation and hypermutation. Many of these processes, particularly hypermutation, may lead to oncogenic mutations. Indeed, many types of lymphomas originate from defects during hypermutation occurring in the germinal centers. Mutations in NFkappaB signaling molecules and in negative regulators such as CYLD and A20 have been identified in B cell lymphomas. These deubiquitinating enzymes remove activating...B-lymphocytes participate in immune responses that require their proliferation, differen- tiation and hypermutation. Many of these processes, particularly hypermutation, may lead to oncogenic mutations. Indeed, many types of lymphomas originate from defects during hypermutation occurring in the germinal centers. Mutations in NFkappaB signaling molecules and in negative regulators such as CYLD and A20 have been identified in B cell lymphomas. These deubiquitinating enzymes remove activating lysine-63 linked ubiquitin chains from numerous NFkappaB signaling molecules, including the I!B molecule and the oncogene Bcl-3 thus controlling their activity. This project aims at investigating the role of CYLD and A20 in lymphomagenesis using mice with conditional mutations in CYLD and A20 in B cells. These mice will be exposed to conditions that favor lym- phoma development, such as overexpression of the oncogenes Bcl-3 and/or Bcl-6. Our studies will contribute to the understanding of the mechanisms leading to B cell lym- phoma development potentially setting the ground for novel therapeutic interventions.» weiterlesen» einklappen