Autoimmune disease and lymphoma development based on Id-driven T-B collaboration.
The aim of this project is to increase our understanding of normal immune regulation mechanism. Further, to understand how immune dysregulation can cause development of autoimmune diseases and B cell lymphomas. Post germinal B cells can present idiotypic(Id) peptides derived from B cell receptor (BCR) variable(V) regions on their MHC class II molecules to T cells. When this interaction goes awry, it is results in development of autoimmune disease and B cell lymphoma. WE have developed a double transgenic mice NocturnXtg46, which harbor both Id+ B cells and Id specific T cells. This allows us to study the chronic Id-driven autoimmunity and B cell lymphoma. This application describes experiments aimed at evaluating the the Auto immunity and lymphoma development in our double transgenic mouse model (NocturnXtg46) and also the tumorigenic potential of expanded B and T cell clones that arise in the spleens and lymph nodes of Nocturn x tg46 mice by transferring them into immunodeficient mice which lacks B and T cells.
Value to society: we have developed an animal model with very high relevance to the disease process that links human autoimmune disease and lymphoma. In experiments generated in FOTS ID 7414, we have shown that such mice develop auto-antibodies already at three months of age, but clinical symptoms of disease at early stage are rare and mild, such as hair loss on the snout in one mouse, and somewhat slower weight gain compared to controls.
We will use a total of 910 mouse in this project. We will reduce the animals used for secondary and later passages to the absolute lowest necessary. In addition, we will reduce the cell dose in the subsequent passage experiments, such that we avoid a very exaggerated disease course, which would put more strain on the animals. We will complement our studies with assays of invitro characterization and expansion of the lines in culture.
Value to society: we have developed an animal model with very high relevance to the disease process that links human autoimmune disease and lymphoma. In experiments generated in FOTS ID 7414, we have shown that such mice develop auto-antibodies already at three months of age, but clinical symptoms of disease at early stage are rare and mild, such as hair loss on the snout in one mouse, and somewhat slower weight gain compared to controls.
We will use a total of 910 mouse in this project. We will reduce the animals used for secondary and later passages to the absolute lowest necessary. In addition, we will reduce the cell dose in the subsequent passage experiments, such that we avoid a very exaggerated disease course, which would put more strain on the animals. We will complement our studies with assays of invitro characterization and expansion of the lines in culture.