Christopher C. Goodnow
Understanding the mechanism of immunological tolerance to self antigens remains a fundamental problem in immunology, with important practical relevance for autoimmunity, organ transplantation, and the development of vaccines. Our group uses transgenic mice carrying rearranged antigen-receptor genes to provide a window into the events involved in this process, by allowing the development and fate of antigen-specific B lymphocytes to be followed. In the B cell lineage, as in T cells, self-reactive cells undergo several distinct fates; they can be physically eliminated, functionally inactivated, or they can persist unchanged or become activated. We hope to achieve a precise understanding of the cellular and molecualr events leading to lymphocyte deletion, anergy or activation by using a number of approaches:
(i) Manipulate the structure and expression of self antigens in transgenic mice.
(ii) Analyze the biochemical signalling events accompanying induction of B cell deletion or anergy, and the subsequent nuclear events leading either to death of the cell (deletion) or inhibition of terminal differentiation (the basis of anergy).
(iii) Structure/function analysis of the B cell antigen receptor by overexpressing mutated receptor components in transgenic mice.