Development of the gene therapy model for allergic diseases

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BCL6-KO mice display no germinal center formation and severe allergic inflammation with eosinophilic infiltration. We found that one of the target gene of BCL6 in T cells is the IL-5 gene. In this project, we investigated the functional role of BCL6 in memory B cell development and tried to develop the gene therapy model for allergic diseases by establishing model animals in which expression of BCL6 is controlled. We show that (1) BCL6-KO mice produced control levels of secondary IgG1 antibodies, and generated transferable IgG1 memory B cells in the spleen. Mutation in the V-hedvy gene was nil in those memory B cells. We have established transgenic mice carrying the Ig-BCL6, and the germinal center formation and memory responses were augmented in transgenic mice. Therefore, Bcl6 is essential for somatic hypermutation and generation of memory B cells in germinal centers. (2) We have established transgenic mice carrying the lck-BCL6 gene. When splenic T cells from lck-BCL6 mice were stimulated with anti-CD3 antibody, IL-5 production was specifically suppressed. Those lck-BCL6 mice were mated with BCL6-KO mice and the allergic inflammation in BCL6-KO mice was completely controlled. We have established the gene transfer method using virus vectors. We wish to develop the efficient gene therapy method for allergic diseases near future.