Klinman N R, Schrater A F, Katz D H
J Immunol. 1981 May;126(5):1970-3.
In vitro studies have indicated that immature B cells at a specific stage in clonal maturation are exquisitely susceptible to tolerance induction by antigens and antigen concentrations that have no effect on mature B cells. In order to determine if a similar phenomenon obtains for B cells in vivo, mice were tolerized with DNP-D-GL and their splenic and bone marrow B cells were carefully washed and analyzed for responsiveness in the splenic focus system. The results demonstrate that, whereas the treated mice themselves become rapidly unresponsive to either DNP or TNP on a heterologous carrier, a measurable decrease in the frequency of splenic DNP-responsive B cells occurs only very slowly with a half-life of approximately 2 wk and TNP-responsive splenic B cells are only marginally, if at all, affected. A progressive decrease in DNP-responsive bone marrow B cells is also observed and occurs at a somewhat more rapid rate than the decrease in splenic B cells. The rate of decrease of splenic precursor cells is totally consistent with the normal attrition of mature B cells in the absence of newly generated DNP-specific B cells. Thus, in vivo tolerance, like in vitro tolerance may only eliminate immature B cells as they emerge from their stem cell pool and has no effect on mature resident B cells. This conclusion is consistent with the additional finding that 1 mo after tolerance induction, the majority of remaining DNP-responsive B cells in the bone marrow is found in very early precursors that have not, as yet, acquired their immunoglobulin receptors. Finally, the exquisite specificity of this tolerance induction would be totally consistent with a physiologic role for a clonal abortion mechanism that could specifically eliminate self-reactive B cells while leaving essentially intact the B cell repertoire responsive to non-self determinants.
体外研究表明，克隆成熟特定阶段的未成熟B细胞极易受到抗原及抗原浓度的耐受诱导，而这些抗原和抗原浓度对成熟B细胞并无影响。为了确定体内B细胞是否也存在类似现象，用二硝基苯 - D - 半乳糖（DNP - D - GL）使小鼠产生耐受，然后仔细洗涤其脾脏和骨髓B细胞，并在脾脏聚焦系统中分析其反应性。结果表明，虽然经处理的小鼠自身很快对异源载体上的二硝基苯（DNP）或三硝基苯（TNP）无反应，但脾脏中对DNP有反应的B细胞频率仅非常缓慢地下降，半衰期约为2周，而对TNP有反应的脾脏B细胞即使有影响也微乎其微。同时观察到骨髓中对DNP有反应的B细胞也在逐渐减少，且其减少速度比脾脏B细胞稍快。脾脏前体细胞的减少速率与在没有新产生的DNP特异性B细胞时成熟B细胞的正常损耗完全一致。因此，体内耐受与体外耐受一样，可能仅在未成熟B细胞从干细胞库中出现时将其消除，而对成熟的驻留B细胞没有影响。这一结论与另一项发现一致，即在耐受诱导1个月后，骨髓中大部分剩余的对DNP有反应的B细胞存在于尚未获得免疫球蛋白受体的非常早期的前体细胞中。最后，这种耐受诱导的高度特异性与克隆流产机制的生理作用完全相符，该机制可以特异性地消除自身反应性B细胞，同时基本保持对非自身决定簇有反应的B细胞库完整。
