Increased susceptibility of cord blood B lymphocytes to undergo spontaneous apoptosis.
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 microg/ml) was further added. Thus, alterations in Bcl-2 or serum BAFF level may explain the increased rate of cord blood B cell apoptosis.
Kessel
A
A
Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Faculty of Medicine Technion, Haifa, Israel. aharon.kessel@b-zion.org.il
Yehudai
D
D
Peri
R
R
Pavlotzky
E
E
Bamberger
E
E
Tov
N
N
Toubi
E
E
D000328:Adult; D000704:Analysis of Variance; D018941:Antigens, CD19 / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018956:CD5 Antigens / Q000276:immunology; D002478:Cells, Cultured; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D018941:Antigens, CD19; D053264:B-Cell Activating Factor; D018956:CD5 Antigens; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4