Klinman N R
J Exp Med. 1972 Aug 1;136(2):241-60. doi: 10.1084/jem.136.2.241.
Cell transfers to carrier-immunized irradiated mice have permitted an analysis of the in vitro stimulation of clonal precursors of anti-2,4-dinitrophenyl (DNP) antibody-producing cells derived from both immune and nonimmune mice. The results indicate that: (a) carrier-specific enhancement is obligatory for stimulation of primary precursor cells and increases both the size and number of detectable foci derived from secondary precursors. (b) This carrier-specific enhancement is most apparent in the stimulation of precursors of high-affinity antibody producer cells. (c) The antibody produced by primary foci, like that of secondary foci, appears homogeneous. (d) The frequency of clonal precursors in normal spleens is 38% that in spleens from mice 4-8 months after immunization, and the number of such precursors in normal spleens can be reduced fivefold by specific suppression of donor mice with soluble antigen. (e) The average of association constants of primary monofocal antibodies, like that of primary serum antibody produced in carrier-primed mice, is less than 10-fold lower than that of secondary clonal or serum antibody. (f) The affinity of primary monofocal antibodies shows a slight dependence on stimulating antigen concentration; however, a minimum threshold affinity consonant with stimulation is apparent. (g) Free hapten inhibits antigenic stimulation of primary precursor cells at a much lower concentration than is required for the inhibition of secondary precursors. These results are interpreted as indicating that (a) primary stimulation, like secondary stimulation, results from the selective stimulation by antigen of a population of cells differing from one another in their potential antibody product but each having only a single such product; (b) the antigen receptors of primary cells interact with antigen as if they are monovalent while receptors of secondary cells evidence multivalence; (c) antigenic stimulation appears to require both a relatively high affinity of receptors for bound antigen and an interlinking of receptors through such antigen; stimulation is thus seen as resulting from a stabilization of receptors within antigen-receptor aggregates to the cell surface; (d) T-cells appear to serve both in cross-linking antigens and in amplifying the size of stimulated clones.
将细胞转移至经载体免疫的受辐照小鼠体内，使得对源自免疫和非免疫小鼠的抗2,4 - 二硝基苯基（DNP）抗体产生细胞的克隆前体细胞的体外刺激进行分析成为可能。结果表明：（a）载体特异性增强对于初级前体细胞的刺激是必不可少的，并且会增加源自次级前体细胞的可检测灶的大小和数量。（b）这种载体特异性增强在高亲和力抗体产生细胞前体细胞的刺激中最为明显。（c）初级灶产生的抗体与次级灶产生的抗体一样，似乎是同质的。（d）正常脾脏中克隆前体细胞的频率是免疫后4 - 8个月小鼠脾脏中克隆前体细胞频率的38%，通过用可溶性抗原特异性抑制供体小鼠，正常脾脏中此类前体细胞的数量可减少五倍。（e）初级单灶抗体的结合常数平均值与在载体致敏小鼠中产生的初级血清抗体的结合常数平均值一样，比次级克隆抗体或血清抗体的结合常数平均值低不到10倍。（f）初级单灶抗体的亲和力对刺激抗原浓度有轻微依赖性；然而，与刺激相一致的最低阈值亲和力是明显的。（g）游离半抗原以比抑制次级前体细胞所需浓度低得多的浓度抑制初级前体细胞的抗原刺激。这些结果被解释为表明：（a）初级刺激与次级刺激一样，是由抗原对一群细胞的选择性刺激导致的，这群细胞在其潜在抗体产物上彼此不同，但每个细胞只有一种这样的产物；（b）初级细胞的抗原受体与抗原相互作用时似乎是单价的，而次级细胞的受体表现出多价性；（c）抗原刺激似乎既需要受体对结合抗原具有相对较高的亲和力，又需要通过这种抗原使受体相互连接；因此，刺激被视为是由抗原 - 受体聚集体内的受体向细胞表面的稳定化导致的；（d）T细胞似乎既参与交联抗原，又参与扩大受刺激克隆的大小。
