In the last year, enormous progress has been made in defining molecules which are central in delivering signals to B cells through T-B collaboration -- most notably, the ligand for the B cell surface molecule, CD40, was discovered. It is clear that the CD40 ligand is central in inducing immunoglobulin switch recombination; however, it now appears that this molecule is important in directing several aspects of B cell differentiation. Two other lymphocyte triggering molecules with homology to the CD40 ligand have more recently been cloned (the CD27 ligand and the CD30 ligand). A logical place to start to define signals responsible for the induction of switch recombination are with these newly discovered lymphocyte triggering molecules. Thus, the goals of the proposed research are to 1) to define the role(s) that CD40L/CD27L/CD30L play (alone or together) in inducing various aspects of B cell differentiation and 2) to identify specific gene products which contribute to or are responsible for eventual immunoglobulin switch recombination.
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