International Immunology, Vol. 12, No. 2, 123-132,
February 2000
© 2000 Japanese Society for Immunology
Janus kinase 3 (Jak3) is essential for common cytokine receptor 
chain (c)-dependent signaling: comparative analysis of c, Jak3, and c and Jak3 double-deficient mice
Department of Internal Medicine II, Chiba University School of Medicine, Chiba 260-8670, Japan
1 Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
2 Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA
Correspondence to: H. Nakajima, Department of Internal Medicine II, Chiba University School of Medicine, 1-8-1 Inohana, Chiba City, Chiba 260-8670, Japan
The common cytokine receptor 
chain (c) is an essential receptor component for IL-2, IL-4, IL-7, IL-9 and IL-15, and thereby c-deficient mice exhibit impaired T cell and B cell development. The Janus family tyrosine kinase 3 (Jak3) is known to be associated with c, and the reported phenotypes of c-deficient (c–) and Jak3-deficient (Jak3–) mice are similar, indicating that Jak3 is an essential transducer of c-dependent signals. Nevertheless, certain differences have been suggested related to the range of actions of c and Jak3. To clarify whether c-dependent cytokines can partially transduce their signals without Jak3, we compared lymphocyte development in c–, Jak3–, and c and Jak3 double-deficient (c–Jak3–) mice in the same genetic background. With the exception that T and B cells in Jak3– mice express high levels of c, the defects in thymocyte and peripheral T cell and B cell development are indistinguishable among c–, Jak3– and c–Jak3– mice. Interestingly, although Bcl-2 induction was previously suggested to be Jak3-independent, IL-7 cannot induce Bcl-2 expression in CD4 single-positive (SP) thymocytes in either c– or Jak3– mice nor can IL-7 rescue CD4 SP thymocytes from dexamethasone-induced cell death in c– or Jak3– mice. These results indicate that Jak3 is absolutely essential for c-dependent T cell and B cell development, and for c-dependent prevention of thymocyte apoptosis.
Keywords: apoptosis, Bcl-2, common cytokine receptor chain, Jak3, knockout mice
The first two authors contributed equally to this work
Transmitting editor: S. L. Swain
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