Increased susceptibility of cord blood B lymphocytes to undergo spontaneous apoptosis

Abstract

Summary: In this study, we compared the rate of spontaneous apoptosis of B cells from umbilical cord blood with adult B cells and assessed the role of Bcl-2, CD5, interleukin (IL)-4 and B cell-activating factor in B cell spontaneous apoptosis. We found that spontaneous apoptosis of cultured B cells, as assessed by utilizing annexin-V binding, was significantly higher in cord blood than in healthy adult individuals (77·5; 95 CI, 73·5–81·5 versus 59·2; 95 CI, 54–64, respectively, P < 0·0001) and further confirmed by 4′ 6-diamidino-2-phenylindole, dihydrochloride (DAPI) staining. Whereas the expression of B cell-activating factor from the tumour necrosis factor family (BAFF) receptor mRNA was similar in B cells from adults and cord blood, we detected lower levels of circulating BAFF in the serum of cord blood (0·68 ± 0·13 ng versus 1·83 ± 0·54 ng, P = 0·01). The latter may explain, in part, our observation of lower levels of mean fluorescence intensity of Bcl-2 in cord B cells compared with adults (1·6 ± 0·9 versus 2·85 ± 1·3, P = 0·033). CD19+ CD5+ B cells from cord blood underwent a lower rate of apoptosis in comparison to CD19+ CD5– B cells (25·1 ± 9·3%versus 58·5 ± 12·5%, P < 0·0001). This pattern of sensitivity was comparable in adult blood (15 ± 5·5%versus 22·7 ± 9·3%, P = 0·01). Nevertheless, the rate of apoptosis was higher in CD19+ CD5+ from cord blood compared to CD19+ CD5+ from adults (25·1 ± 9·3%versus 15 ± 5·5%, P = 0·0013). The addition of rIL-4 (10 u/ml) to cultured cells decreased B cell apoptosis in a similar fashion in both cord and adults blood. This rescue was strengthened when BAFF (100 µg/ml) was further added. Thus, alterations in Bcl-2 or serum BAFF level may explain the increased rate of cord blood B cell apoptosis.