Expression and Localization of the Calcium-Mobilizing Molecules, Calcineurin and NFAT in Germinal Center B Cells

Intracellular signaling via the B-cell antigen receptor (BCR) regulates cellular dynamics in B cells, in a similar way to signaling via the T-cell receptor (TCR) in T lymphocytes. Cross-linking of BCR increases Ca2+ influx as a first event, which then activates Ca2+-dependent signaling molecules. Calcineurin and nuclear factor of activated T cell (NFAT) are Ca2+-mobilizing elements that are considered to be important in regulating proliferation of T cells. However, little is known about their expression in B cells, especially in the germinal center, where apoptosis and proliferation of B cells actively take place for clonal selection. We investigated the expression and the localization of Ca2+-mobilizing molecules, including calcineurin and NFAT, in germinal center B cells by immunofluorescence. The results revealed a dramatic increase of intracellular Ca2+, a constitutive expression of calcineurin, and a unique localization of NFATc2. Interestingly, several germinal center B cells expressed nuclear-imported NFATc2, which suggests the activation of NFATc2 and its involvement in the dynamics of B cells in the germinal center. Moreover, double immunofluorescence experiments demonstrated the co-expression of NFAT and cleaved-caspase 3 in apoptotic B cells of the germinal center. Thus, these results indicate that NFAT may participate in the regulation of B-cell dynamics such as apoptosis in the germinal center.