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 isoforms on all nucleated hematopoietic cells, resulting from alternative splicing of variable exons. We generated mice with a mutation in the variable CD45 exon 6, using homologous recombination. In mice homozygous for the CD45-exon6 mutation, B cells and most T cells did not express CD45. Development of B cells appeared normal, although Igμ-induced proliferation was completely abrogated. Thymocyte maturation was blocked at the transitional stage from Immature CD4 +CD8 + to mature CD4 + or CD8 + cells, and only a few T cells could be detected in peripheral lymphoid organs. Clonal deletion of superantigen-reactive T cells still occurred. Cytotoxic T cell responses to lymphocytic choriomeningitis virus were absent in CD45-exon6 −/− mice. These data imply that CD45 is differentially required for the development and function of B and T lymphocytes.