Kearney R, Andrews J, Johnstone S
Aust J Exp Biol Med Sci. 1986 Feb;64 ( Pt 1):19-35. doi: 10.1038/icb.1986.3.
Prior treatment (priming) with a weakly immunogenic dose of Type III pneumococcal polysaccharide (SIII) results in the development of an antigen-specific state of unresponsiveness termed low-dose paralysis which is believed to be mediated by suppressor T cells. The present findings show that the passive administration of functionally distinct non-complement-fixing (NCF) IgM anti-SIII antibodies either in monoclonal form or from protein-A absorbed immune serum could significantly suppress the direct plaque-forming cell (PFC) response to an immunogenic dose of SIII administered concurrently. The degree of suppression was comparable with that induced by low-dose paralysis. Low-dose paralysis was consistently induced in athymic (nude) mice 4 days, but not 3 days, after priming with a low dose of SIII, and was associated with the delayed appearance of NCF-IgM anti-SIII in the serum of athymic mice. In contrast, low-dose paralysis was readily induced in normal BALB/c mice 3 days after priming when NCF-IgM anti-SIII antibodies were present. Comparable inhibiton of the direct anti-SIII PFC response was observed when Concanavalin A (Con A) or NCF-IgM anti-SIII serum was administered with SIII antigen. That Con A and NCF-IgM anti-SIII together did not produce additive suppression was attributed to the adsorption of NCF-IgM anti-SIII antibodies to Con A. Complement-dependent single radial haemolysis mediated by CF hybrid IgM/A or CF-IgM anti-SIII serum was blocked by monoclonal NCF-IgM or IgA anti-SIII antibodies and indicated that each of the antibodies was specific for the same SIII-determinant. Evidence is presented to show that low-dose paralysis in the CF-IgM response to SIII is not mediated by suppressor T cells but can be attributed to highly avid NCF-IgM anti-SIII antibodies, formed preferentially to low doses of SIII, being able to reduce the immunogenicity of SIII administered subsequently. We propose that low-dose paralysis to SIII is the result of an immunobiological function of highly avid NCF-IgM anti-SIII antibodies which not only confer resistance against capsulated pneumococci but preferentially bind soluble SIII-antigen to reduce its immunogenicity and thereby protect specific CF-IgM positive B cells from being rendered tolerant by direct contact with higher doses of SIII antigen.
用低免疫原性剂量的Ⅲ型肺炎球菌多糖（SIII）进行预先处理（致敏）会导致一种称为低剂量麻痹的抗原特异性无反应状态的出现，这种状态被认为是由抑制性T细胞介导的。目前的研究结果表明，以单克隆形式或从蛋白A吸附的免疫血清中被动给予功能不同的非补体结合（NCF）IgM抗SIII抗体，可显著抑制对同时给予的免疫原性剂量SIII的直接空斑形成细胞（PFC）反应。抑制程度与低剂量麻痹诱导的程度相当。用低剂量SIII致敏后4天而非3天，无胸腺（裸）小鼠持续诱导出低剂量麻痹，且与无胸腺小鼠血清中NCF-IgM抗SIII的延迟出现有关。相反，当存在NCF-IgM抗SIII抗体时，正常BALB/c小鼠在致敏后3天很容易诱导出低剂量麻痹。当伴刀豆球蛋白A（Con A）或NCF-IgM抗SIII血清与SIII抗原一起给药时，观察到对直接抗SIII PFC反应有类似的抑制作用。Con A和NCF-IgM抗SIII共同作用未产生累加抑制作用，这归因于NCF-IgM抗SIII抗体被Con A吸附。由CF杂交IgM/A或CF-IgM抗SIII血清介导的补体依赖性单扩散溶血被单克隆NCF-IgM或IgA抗SIII抗体阻断，表明每种抗体对相同的SIII决定簇具有特异性。有证据表明，对SIII的CF-IgM反应中的低剂量麻痹不是由抑制性T细胞介导的，而是可归因于优先针对低剂量SIII形成的高亲和力NCF-IgM抗SIII抗体，能够降低随后给予的SIII的免疫原性。我们提出，对SIII的低剂量麻痹是高亲和力NCF-IgM抗SIII抗体免疫生物学功能的结果，这些抗体不仅赋予对荚膜肺炎球菌的抗性，而且优先结合可溶性SIII抗原以降低其免疫原性，从而保护特定的CF-IgM阳性B细胞不被更高剂量的SIII抗原直接接触而导致耐受。
