Davie J M, Paul W E, Katz D H, Benacerraf B
J Exp Med. 1972 Sep 1;136(3):426-38. doi: 10.1084/jem.136.3.426.
The induction of tolerance in guinea pigs with a 2,4-dinitrophenyl (DNP) derivative of a copolymer of copolymer of D-glutamic acid and D-lysine (D-GL) leads to a preferential depression of the capacity to produce high affinity anti-DNP antibody in response to immunization with DNP-guinea pig albumin. Thus, immunization 2 wk after tolerance induction with 3 mg of DNP-D-GL results in an immune response in which individual plaque-forming cells (PFC) secreting high affinity anti-DNP antibody are absent and in which the affinity of circulating anti-DNP antibody is reduced. A similar, but less marked, suppression is seen when 0.3 mg of DNP-D-GL is used for tolerance induction. If immunization is delayed until 2 months after tolerance induction, then suppression is restricted to the highest avidity PFC group. Our data is consistent with a state of tolerance in the pool of precursors of anti-DNP antibody-secreting cells induced as a result of their interaction with DNP-D-GL in the absence of specific "helper" cells, which appear to be lacking for DNP-D-GL. In such a situation, the affinity of receptors on precursor cells for tolerogen and the concentration of tolerogen appear to be crucial determinants of whether an individual cell will become tolerant.
用D-谷氨酸和D-赖氨酸的共聚物（D-GL）的2,4-二硝基苯基（DNP）衍生物诱导豚鼠产生耐受性，会导致在对DNP-豚鼠白蛋白免疫应答时，产生高亲和力抗DNP抗体的能力受到优先抑制。因此，在用3mg DNP-D-GL诱导耐受性2周后进行免疫，会引发一种免疫应答，即不存在分泌高亲和力抗DNP抗体的单个噬斑形成细胞（PFC），且循环抗DNP抗体的亲和力降低。当用0.3mg DNP-D-GL进行耐受性诱导时，会观察到类似但不太明显的抑制作用。如果将免疫推迟到耐受性诱导后2个月，那么抑制作用就仅限于最高亲和力的PFC组。我们的数据与抗DNP抗体分泌细胞前体池中由于在缺乏特异性“辅助”细胞（DNP-D-GL似乎缺乏这种细胞）的情况下与DNP-D-GL相互作用而诱导产生的耐受状态一致。在这种情况下，前体细胞上耐受原受体的亲和力以及耐受原的浓度似乎是单个细胞是否会产生耐受的关键决定因素。
