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 Ig mu-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.
Kishihara
K
K
Amgen Institute, Toronto, Ontario, Canada.
Penninger
J
J
Wallace
V A
VA
Kündig
T M
TM
Kawai
K
K
Wakeham
A
A
Timms
E
E
Pfeffer
K
K
Ohashi
P S
PS
Thomas
M L
ML
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005091:Exons; D007148:Immunoglobulin mu-Chains; D017493:Leukocyte Common Antigens / Q000235:genetics*; D051379:Mice; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D007148:Immunoglobulin mu-Chains; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases