Mitochondria Na(+)-Ca(2+) exchange (NCX(mit)) was first discovered by Carafoli et al. in 1974. Thereafter, the mechanisms and roles of NCX(mit) have been extensively studied. We review NCX(mit) in cardiomyocytes and lymphocytes by presenting our recent studies on it. Studies of NCX(mit) in rat ventricular cells demonstrated that NCX(mit) is voltage dependent and electrogenic. A targeted knockdown and knockout of NCLX in HL-1 cardiomyocytes and B lymphocytes, respectively, significantly reduced the NCX(mit) activity, indicating that NCLX is a major component of NCX(mit) in these cells. The store-operated Ca(2+) entry was greatly attenuated in NCLX knockout lymphocytes, suggesting that substantial amount of Ca(2+) enters into mitochondria and is released to cytosol via NCX(mit). NCX(mit) or NCLX has pivotal roles in Ca(2+) handling in mitochondria and cytoplasm.
The positive and negative selection of antigen-reactive B cells take place in the germinal center (GC) during an immune responses. However, the precise molecular mechanisms underlying these selection machineries, including the involvement of antigen receptor signaling molecules, remain to be elucidated. We found that expression levels of Igα and Igβ, which are the essential components of B cell antigen-receptor complex, were differentially regulated in GC B cells and that the expression of Igβ was more prominently down-regulated in a portion of GC B cells. The suppression of Igβ down-regulation reduced the number of GL7+GC B cells and the affinity maturation in T-dependent responses was markedly impaired. In addition, the disease phenotypes in autoimmune-prone mice were ameliorated by blocking of Igβ down-regulation. These results suggest that Igβ down-regulation is involved in the normal positive selection in GC and the accumulation of autoreactive B cells in autoimmune-prone mice.
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