Department of Paediatrics, College of Medicine, Chungnam National University, Jung-gu, Daejeon, Korea.
J Interferon Cytokine Res. 2011 May;31(5):441-9. doi: 10.1089/jir.2010.0020. Epub 2011 Feb 3.
CD19(+)CD5(+) regulatory B cells produce transforming growth factor β (TGF-β) in both mouse and human B-cell leukemias. In this study, TGF-β was uniquely produced by normal human regulatory B cells. TGF-β-producing regulatory B-cell (Br3) responses were characterized through allergic responses to cow's milk. In total, 10 subjects allergic to milk and 13 milk-tolerant subjects were selected following double-blinded, placebo-controlled food challenges. Their peripheral blood mononuclear cells were stimulated in vitro with casein. Following allergen stimulation, the percentage of Br3s among CD5(+) B cells decreased from 11.5% ± 13.7% to 8.0% ± 9.6% (P = 0.042, n = 5) in the milk-allergy group and increased from 14.7% ± 15.6% to 18.9% ± 20.1% (P = 0.006, n = 7) in the milk-tolerant group. However, the numbers of Br3s increased only in the milk-tolerant group, from 1,954 ± 1,058 to 4,548 ± 1,846 per well (P = 0.026), whereas the numbers of Br3s in the milk-allergy group were unchanged [2,596 ± 823 to 2,777 ± 802 per well (P = 0.734)]. The numbers of apoptotic events were similar to the numbers of total Br3 responses. The percentage of non-TGF-β-producing CD5(+) B cells with apoptotic changes increased from 13.4% ± 17.1% to 16.4% ± 20.3% (P = 0.047, n = 5) in the milk-allergy group and remained unchanged [from 9.9% ± 11.9% to 9.3% ± 11.4% (P = 0.099, n = 7)] in the milk-tolerant group. Using carboxyfluorescein succinimidyl ester labeling, we observed that the percentage of proliferating Br3s among CD5(+) B cells was unchanged [from 6.1% ± 2.8% to 6.4% ± 2.9% (P = 0.145)] in the milk-allergy group and increased from 6.8% ± 3.9% to 10.2% ± 5.3% (P = 0.024) in the milk-tolerant group. In conclusion, Br3s proliferated in response to allergen stimulation in the milk-tolerant group and not in the milk-allergy group. TGF-β-producing regulatory B cells (Br3) may be involved in allergy tolerance by negatively regulating the immune system with TGF-β, and this negative regulation may be controlled by apoptosis.
CD19(+)CD5(+) 调节性 B 细胞在小鼠和人类 B 细胞白血病中产生转化生长因子 β (TGF-β)。在这项研究中，TGF-β 是由正常人类调节性 B 细胞特异性产生的。通过对牛奶过敏反应来研究 TGF-β 产生的调节性 B 细胞 (Br3) 反应。总共选择了 10 名对牛奶过敏和 13 名对牛奶耐受的受试者，他们在双盲、安慰剂对照的食物挑战后进行了选择。他们的外周血单核细胞用酪蛋白体外刺激。在变应原刺激后，牛奶过敏组 CD5(+)B 细胞中 Br3s 的百分比从 11.5%±13.7%降至 8.0%±9.6%（P=0.042，n=5），而牛奶耐受组从 14.7%±15.6%增至 18.9%±20.1%（P=0.006，n=7）。然而，仅在牛奶耐受组中 Br3s 的数量增加，从每孔 1,954±1,058 个增加到 4,548±1,846 个（P=0.026），而牛奶过敏组中的 Br3s 数量不变[每孔 2,596±823 个增加到 2,777±802 个（P=0.734）]。凋亡事件的数量与总 Br3 反应的数量相似。具有凋亡变化的非 TGF-β 产生的 CD5(+)B 细胞的百分比从牛奶过敏组的 13.4%±17.1%增加到 16.4%±20.3%（P=0.047，n=5），而牛奶耐受组保持不变[从 9.9%±11.9%到 9.3%±11.4%（P=0.099，n=7）]。使用羧基荧光素琥珀酰亚胺酯标记，我们观察到 CD5(+)B 细胞中增殖 Br3s 的百分比在牛奶过敏组中没有变化[从 6.1%±2.8%到 6.4%±2.9%（P=0.145）]，而在牛奶耐受组中从 6.8%±3.9%增加到 10.2%±5.3%（P=0.024）。总之，Br3s 在牛奶耐受组中对变应原刺激产生增殖，而在牛奶过敏组中则没有。产生 TGF-β 的调节性 B 细胞 (Br3) 可能通过 TGF-β 负向调节免疫系统参与过敏耐受，这种负向调节可能受到细胞凋亡的控制。
