Klinman N R
J Exp Med. 1971 May 1;133(5):963-72. doi: 10.1084/jem.133.5.963.
The in vitro secondary stimulation of the production of anti-hapten antibody has been analyzed with a view to elucidating the role of the carrier molecule and cell-to-cell interactions in this response. Stimulation was carried out on fragment cultures of the spleens of irradiated BALB/c mice which had been reconstituted with 3-4 x 10(7) spleen cells from isologous mice previously immunized with DNP-Hy. The results indicated that the response was maximized by stimulation with DNP-Hy, the homologous complex, however anti-DNP antibody production could be obtained by stimulation with DNP on several nonhomologous carriers including poly-D-lysine, a poor immunogen. The results also indicated that while DNP-Hy and DNP-nonhomologous-carrier complexes were stimulatory at equally low DNP concentrations, at DNP concentrations over 10(-6)M DNP-Hy was stimulatory, while DNP on nonhomologous carriers was inhibitory. The results are interpreted as indicating that: (a) the affinity of the antigen-cell interaction is more likely determined by multivalent binding than by carrier recognition, (b) that a stimulatory interaction of a polyvalent antigen with a B-lymphocyte cannot be excluded, (c) that if cell-to-cell interaction is necessary for stimulation, then both cells may recognize the same determinant, and (d) that the marked enhancement of antigenic stimulation attributable to carrier recognition may result from stimulatory interactions of cells recognizing different antigenic determinants. A mechanism is postulated whereby stimulation is dependent on the formation of stable complexes resulting from two cells sharing in the binding of numerous antigen molecules. Cells recognizing carrier determinants would increase the probability of such interactions particularly at high antigen concentrations.
为了阐明载体分子和细胞间相互作用在抗半抗原抗体产生的体外二次刺激反应中的作用，我们对此进行了分析。刺激是在受照射的BALB/c小鼠脾脏的片段培养物上进行的，这些小鼠已用先前用DNP-Hy免疫的同基因小鼠的3-4×10⁷个脾细胞进行了重建。结果表明，用同源复合物DNP-Hy刺激可使反应最大化，然而，通过用DNP刺激几种非同源载体（包括弱免疫原性的聚-D-赖氨酸）也可获得抗DNP抗体的产生。结果还表明，虽然DNP-Hy和DNP-非同源载体复合物在同样低的DNP浓度下具有刺激作用，但在DNP浓度超过10⁻⁶M时，DNP-Hy具有刺激作用，而DNP在非同源载体上则具有抑制作用。这些结果被解释为表明：（a）抗原-细胞相互作用的亲和力更可能由多价结合决定而非载体识别，（b）不能排除多价抗原与B淋巴细胞之间的刺激相互作用，（c）如果刺激需要细胞间相互作用，那么两个细胞可能识别相同的决定簇，（d）归因于载体识别的抗原刺激的显著增强可能源于识别不同抗原决定簇的细胞之间的刺激相互作用。我们提出了一种机制，据此刺激依赖于由两个细胞共同结合众多抗原分子而形成的稳定复合物。识别载体决定簇的细胞会增加这种相互作用的概率，特别是在高抗原浓度下。
