An investigation into the e biology and function of the Themis B cell homologue Icb-1. (360G-Wellcome-086339_Z_08_A)

An investigation into the biology and function of the Themis B cell homologue lcb-1 The generation of an effective adaptive immune response to pathogens depends upon the appropriate selection and regulation of antigen-specific lymphocytes. T and B cell development and selection are both driven at different stages by the encounter between antigen receptors (TCRs and BCRs respectively) and target antigens. Positive and negative selection is a function of developmental stage and depends on the strength of the interaction and the presence of accessory signals [1-2]. How these external signals are integrated with the internal milieu leading to death or survival is one of the great mysteries in immunology. Despite the fact that a high effort has been put into studying these processes, many factors and pathways remain unknown. There is therefore an urgent need to understand more about these processes. One of the methods to identify new pathways involved in immune regulation is to introduce mutations into mice using ethyl-nitrosourea (ENU) and then screen for animals carrying immune phenotypes [3). This approach recently lead to the identification of a new gene family including protein Them is (with two other groups) which was shown to be essential in T cell selection [4-6]. lcb-1 is a close homologue to Themis, which is expressed in B cells and cells of the myeloid lineage. lcb-1 is speculated to have similar roles in B cell development. Our laboratory has a longstanding interest in B development and has generated a variety of transgenic tools for studying the positive and negative selections of B cells at the immature stage and during affinity maturation in the germinal centre [7]. The aim of this project is to study the functions of lcb-1.