Differential expression of the B cell-restricted molecule CD22 on neonatal B lymphocytes depending upon antigen stimulation

Abstract

Newborns respond poorly to certain antigens and produce mainly IgM antibodies. By flow cytometry we analyzed on neonatal and adult B cells the expression of CD22, a B cell receptor (BCR)-associated membrane molecule, known as negative modulator of BCR signaling. After T cell-independent (TI-)stimulation with anti-mu F(ab')(2) fragments we found a dramatic decrease in the percentage of neonatal CD22(+) B cells and CD22 mean fluorescence intensity (MFI) shift, whereas adult B cells remained unaffected. Survival and proliferation rates of neonatal B cells were higher compared to adult B cells whereas the degrees of apoptosis and necrosis were comparable. Surprisingly, after stimulation with lower doses of anti-mu apoptosis as well as proliferation increased significantly in contrast to adult B cells. T cell-dependent (TD)-stimulation with anti-CD40 monoclonal antibody and IL-4 resulted in a dramatic increase in the percentage of CD22(+) neonatal B cells in contrast to unaffected adult B cells. CD22 MFI shifts showed no significant changes, respectively. The survival rate was higher for adult B cells, whereas apoptosis and cell death were comparable. These results suggest that TI antigens lower the neonatal BCR signaling threshold via down-regulation of CD22, resulting in hyperresponsive B cells apt to premature apoptosis. On the other hand, up-regulation of CD22 after TD stimulation may allow increased inhibiting influence of CD22 on neonatal BCR signaling, impairing B cell activation and differentiation.