Carrier-induced epitopic suppression is initiated through clonal dominance.
Carrier-induced epitopic suppression is initiated through clonal dominance.
复制标题
载体诱导的表位抑制是通过克隆优势启动的。
作者：
M. Schutze;E. Dériaud;G. Przewlocki;Claude Leclerc
给小鼠注射免疫原性剂量的载体，然后用半抗原载体偶联物免疫，选择性地抑制抗半抗原抗体反应。先前的研究表明，这种表位抑制与载体特异性t细胞的诱导有关，而载体特异性t细胞反过来又可以抑制选择性的抗半抗原反应。在本研究中，我们提出表位抑制实际上是由于克隆优势。用破伤风类毒素等载体免疫可诱导载体特异性B细胞克隆扩增，从而降低半抗原特异性B细胞与抗原反应的可能性。增加tnp -半抗原在缀合物上的密度完全阻止了表位抑制的诱导。此外，使用低半抗原载体浓度挑战载体启动的小鼠增强了抑制的诱导。最后，在载体/半抗原载体免疫前启动半抗原特异性B细胞也消除了这种抑制。这些实验结果支持这样的观点，即表位抑制是通过载体表位特异性克隆的扩增而诱导的，是半抗原和载体表位之间的分子内抗原竞争造成的。基于这些发现，我们提出了B细胞的调节作用，通过它们处理和呈递抗原的能力，它们将对免疫反应的选择产生强烈的影响。
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.