| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Immunoglobuline(Ig) mu chain is expressed on the surface of pre-B cells as a receptor associated with Vpre-B and lambda5 proteins. To understand the physiological function of the pre-B cell receptor, the membrane exon of the mu chain gene and lambda5 gene were disrupted separately in embryonic stem cells by gene targeting, and through the transmission of these mutations into the mouse germ lines, the mutant mice, muMT and lambda5T, were generated. In the B cells from heterozygous muMT mice, muMT allele does not exclude the other heavy chain allele. Homozygous muMT mice lack B cells and B cell development is arrested at or before the stage of large pre-B cells. Similarly, B cell development is inhibited in homozygous lambda5T mice, although this inhibition is leaky, suggesting the presence of lambda5-independent pathway of the B cell development. L chain gene rearrangement occurs in the immature cells in these mutants to the same extent as those cells in normal mice, indicating the initiation of the L chain gene rearrangement is independent of the pre-B cell receptor.
HS1 protein is one of the major substrates of Src-like protein tyrosine kinases and phosphorylated immediately after crosslinking of surface IgM(sIgM)on B cells. The HS1 is also tyrosine-phosphorylated upon the stimulation of T cell receptors(TCR). The HS1 deficient mice, which were generated through gene targeting, showed the impaired ability for thymic negative selection as well as the impaired apoptotic cell death of the B cells induced by the crosslinking of sIgM.This results clearly demonstrated that HS1 is a molecule involved in the signal transduction pathway toward apoptosis that is triggered the antigen receptors.
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