| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Research Abstract |
Transmembrane signal transduction initiated by the B cell antigen receptor (BCR) is essential for various B cell activities, including cell activation, proliferation, anergy and deletion. Signaling through the BCR primarily drives mature B cells into proliferation leading to the expansion of antigen-specific clones. In contrast, immature lymphocytes usually undergo apoptosis, rather than proliferation, upon triggering through BCR.This is the foundation for negative selection, a process that ensures the generation of a self-tolerant immune repertoire during lymphocyte development.
(1) Affinity Maturation in Lyn-deficient Mice with Defective Germinal Center Formation.
One of the phenotypes observed in 1yn-/- mice was a defect in the ability to form germinal centers (GCs). It is believed that Gcs plays an improtant role in afffinity maturation following somatic hypermutation and generation of memory B cells, We clarify whether affinity maturation could occur in 1yn-/- mice. We shows that th
… More
e affinity of Abs produced was comparable to that in wildtype mice.
(2) The death signals from B cell antigen receptor target mitochondria, activating necrotic and apoptotic death cascade in a murine B-cell line, WEHI-23 1 cell.
In order to clarify the molecular mechanism of BCR-mediated cell death, a mouse B-cell lymphoma cell line, WEHI-231, was utilized in the present study. WEHI-231 cell has been used as a model for immature B cells which readily undergo apoptosis upon crosslinkin'g of BCR and for study on the mechanism of clonal selection of B cells. The present works revealed that caspases are activated through BCR signaling to cause apoptosis but mitochondrial alterations and plasma membrane dysfunction, which were also induced by BCR signaling, are not related to the caspase activities. Mitochondrial dysfunction appeared to proceed prior to the plasma membrane and nuclear changes. These data indicate that BCR-mediated death signals primarily cause mitochondrial changes followed by necrotic and apoptotic cascades. Less
|
