Normal B lymphocyte development but impaired T cell maturation in CD45-Exon6 protein tyrosine phosphatase-deficient mice

• Published in: Cell Vol. 74; no. 1; pp. 143 - 156
• Main Authors: Kishihara, Kenji, Penninger, Josef, Wallace, Valerie A., Kündig, Thomas M., Kawal, Kazuhiro, Wakeham, Andrew, Timms, Emma, Pfeffer, Klaus, Ohashi, Pamela S., Thomas, Matthew L., Furlonger, Caren, Paige, Christopher J., Mak, Tak W.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 16.07.1993; Cell Press
• Subjects: Animals; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Biological and medical sciences; CD4 Antigens - immunology; CD8 Antigens - immunology; Cell Differentiation - genetics; Cell Differentiation - immunology; Exons; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Immunoglobulin mu-Chains; Leukocyte Common Antigens - genetics; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Protein Tyrosine Phosphatases - deficiency; Protein Tyrosine Phosphatases - genetics; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - immunology; Alternative splicing; Vertebrata; Mammalia; Mouse; Enzyme; Rodentia; T-Lymphocyte; Development; B-Lymphocyte; Mutation; Cell differentiation; Protein-tyrosine-phosphatase
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(93)90302-7

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.