Schutze M P, Deriaud E, Przewlocki G, LeClerc C
Laboratoire de Biologie des Régulations Immunitaires, Institut Pasteur, Paris, France.
J Immunol. 1989 Apr 15;142(8):2635-40.
Injection of mice with an immunogenic dose of carrier followed by immunization with hapten-carrier conjugate selectively suppresses anti-hapten antibody response. Previous studies have proposed that this epitopic suppression is related to the induction of carrier-specific Ts cells which in turn could inhibit selectively anti-hapten response. In the present study, we propose that the epitopic suppression is in fact due to clonal dominance. Immunization with a carrier such as tetanus toxoid induces a clonal expansion of carrier-specific B cells, thus decreasing the probability of hapten-specific B cells to react with the Ag. Increasing the density of the TNP-hapten on the conjugate has totally prevented the induction of the epitopic suppression. Moreover, using low hapten-carrier concentrations to challenge carrier-primed mice has enhanced the induction of the suppression. Finally, priming hapten-specific B cells before carrier/hapten-carrier immunization has also abrogated the suppression. The results of these experiments support the view that epitopic suppression is induced through the expansion of the clones specific for the carrier epitopes and resulted from intra-molecular antigenic competition between hapten and carrier epitopes. Based on these findings a regulatory role is proposed for B cells, where through their capacity to process and present antigen, they would exercise a strong influence on the selection of immune responses.
给小鼠注射免疫原剂量的载体，随后用半抗原-载体偶联物进行免疫，可选择性地抑制抗半抗原抗体反应。先前的研究提出，这种表位抑制与载体特异性 Ts 细胞的诱导有关，而这些 Ts 细胞反过来又可选择性地抑制抗半抗原反应。在本研究中，我们提出表位抑制实际上是由于克隆优势。用诸如破伤风类毒素之类的载体进行免疫可诱导载体特异性 B 细胞的克隆扩增，从而降低半抗原特异性 B 细胞与抗原反应的概率。增加偶联物上 TNP-半抗原的密度可完全阻止表位抑制的诱导。此外，使用低浓度的半抗原-载体来攻击预先用载体致敏的小鼠可增强抑制作用的诱导。最后，在载体/半抗原-载体免疫之前对半抗原特异性 B 细胞进行致敏也可消除抑制作用。这些实验结果支持这样一种观点，即表位抑制是通过载体表位特异性克隆的扩增诱导产生的，并且是由半抗原和载体表位之间的分子内抗原竞争导致的。基于这些发现，提出了 B 细胞的一种调节作用，即通过其处理和呈递抗原的能力，它们会对免疫反应的选择产生强烈影响。
