Szewczuk M R, Siskind G W
J Exp Med. 1977 Jun 1;145(6):1590-601. doi: 10.1084/jem.145.6.1590.
The ease of tolerance induction in B lymphocytes from fetal, neonatal, and adult mice was studied in vivo, in a cell transfer system, and in vitro. Three different tolerogens were used: ultracentrifuged BGG, DNP(6)-D-GL, and ultracentrifuged DNP(22)-BGG. Irradiated thymectomized mice were reconstituted with B cells from fetal or neonatal liver or adult spleen or bone marrow. The mice were injected with tolerogen 1 day later. They were given normal thymus cells and challenged with either BGG or DNP(44)-BGG between 4 and 14 days after tolerance induction. With BGG no difference in ease of B-cell tolerance induction was observed in mice reconstituted with B cells from 17-day fetal liver, neonatal liver, 8- day-old spleen, adult spleen, or adult bone marrow. B cells from 14-day fetal donors are relatively resistant to tolerance induction. In contrast, with DNP(6)-D-GL and DNP(22)-BGG B cells from neonatal donors were clearly more susceptible to tolerance induction than were B cells from adult donors. Comparable results were obtained in studies on tolerance induction in vitro. Neonatal B cells were more susceptible than adult B cells to tolerance induction upon culture with DNP(6)-D-GL or DNP(22)-BGG. However, neonatal and adult B cells were identical with respect to ease of tolerance induction in vitro with deaggregated BGG. The results suggest that there are multiple mechanisms for B-cell tolerance induction. Immature B cells appear to be more susceptible to tolerance induction by some mechanisms but not by others. It is suggested that immature B cells are more susceptible to tolerance induction with moderately polyvalent antigens such as hapten-carrier conjugates. With antigens like BGG which do not haverepeated epitopes no difference between mature and fetal B cells in regard to ease of tolerance induction is observed. These observations raise questions about the importance of relative ease of tolerance induction in immature B cells as a mechanism controlling the normal induction of self tolerance.
在体内、细胞转移系统及体外研究了来自胎儿、新生小鼠和成年小鼠的B淋巴细胞诱导耐受的难易程度。使用了三种不同的致耐受原：超速离心的BGG、DNP(6)-D-GL和超速离心的DNP(22)-BGG。用来自胎儿或新生肝脏、成年脾脏或骨髓的B细胞重建经照射并切除胸腺的小鼠。1天后给小鼠注射致耐受原。在诱导耐受后4至14天之间，给它们注射正常胸腺细胞并用BGG或DNP(44)-BGG进行攻击。对于BGG，在用来自17天龄胎儿肝脏、新生肝脏、8日龄脾脏、成年脾脏或成年骨髓的B细胞重建的小鼠中，未观察到B细胞诱导耐受的难易程度有差异。来自14天龄胎儿供体的B细胞对诱导耐受相对有抗性。相比之下，对于DNP(6)-D-GL和DNP(22)-BGG，来自新生供体的B细胞比来自成年供体的B细胞明显更易被诱导耐受。在体外诱导耐受的研究中获得了类似结果。在用DNP(6)-D-GL或DNP(22)-BGG培养时，新生B细胞比成年B细胞更易被诱导耐受。然而，就用解聚的BGG在体外诱导耐受的难易程度而言，新生和成年B细胞是相同的。结果表明存在多种B细胞诱导耐受的机制。未成熟B细胞似乎对某些机制诱导的耐受更敏感，但对其他机制则不然。有人提出，未成熟B细胞对中等多价抗原如半抗原-载体缀合物诱导的耐受更敏感。对于像BGG这样没有重复表位的抗原，在诱导耐受的难易程度方面，成熟B细胞和胎儿B细胞之间未观察到差异。这些观察结果引发了关于未成熟B细胞中诱导耐受相对容易程度作为控制自身耐受正常诱导机制的重要性的问题。
