NORMAL B-LYMPHOCYTE DEVELOPMENT BUT IMPAIRED T-CELL MATURATION IN CD45-EXON6 PROTEIN-TYROSINE-PHOSPHATASE DEFICIENT MICE

The transmembrane tyrosine phosphatase CD45 is expressed in multiple i soforms on all nucleated hematopoietic cells, resulting from alternati ve splicing of variable exons. We generated mice with a mutation in th e variable CD45 exon 6, using homologous recombination. In mice homozy gous for the CD45-exon6 mutation, B cells and most T cells did not exp ress CD45. Development of B cells appeared normal, although Igmu-induc ed proliferation was completely abrogated. Thymocyte maturation was bl ocked at the transitional stage from immature CD4+CD8+ to mature CD4or CD8+ cells, and only a few T cells could be detected in peripheral lymphoid organs. Clonal deletion of superantigen-reactive T cells stil l occurred. Cytotoxic T cell responses to lymphocytic choriomeningitis virus were absent in CD45-exon6-/- mice. These data imply that CD45 i s differentially required for the development and function of B and T lymphocytes.