IMMUNE-COMPLEXES CAN TRIGGER SPECIFIC, T-CELL-DEPENDENT, AUTOANTI-IGG ANTIBODY-PRODUCTION IN MICE
IMMUNE-COMPLEXES CAN TRIGGER SPECIFIC, T-CELL-DEPENDENT, AUTOANTI-IGG ANTIBODY-PRODUCTION IN MICE
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DOI：
10.1084/jem.161.1.242
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发表时间：
1985-01-01
影响因子：
15.3
通讯作者：
NEMAZEE, DA
中科院分区：
文献类型：
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作者：
NEMAZEE, DA
用被动给予的同基因IgG（抗对偶氮苯胂酸[anti-Ars]）抗体和可溶性多价形式的抗体相应抗原（与Ars [Lph-Ars]缀合的多血蓝蛋白）联合免疫小鼠，导致特异性自身抗IgG Fc（类风湿因子）产生。免疫反应迅速，仅发现IgM同种型的抗IgG抗体。由于单独用IgG抗体或抗原免疫均不能产生类风湿抗体，因此免疫复合物似乎是免疫原的活性形式。导致最大抗IgG抗体应答的抗体/抗原比率与体外免疫沉淀峰值所需的比率相同，即，等价性应答不需要小鼠先前暴露于外源性提供的抗原。对免疫复合物的反应是特异性的，因为用含IgG 2a的复合物免疫的小鼠产生自身抗IgG 2a，而用含IgG 1的复合物免疫的小鼠产生抗IgG 1，对其他IgG同种型几乎没有反应性。阻断其补体结合能力的IgG 2a比天然IgG 2a更有效地引发抗IgG 2a应答，表明补体系统在调节抗IgG 2a应答中可能起作用。免疫复合物诱导类风湿因子的产生可以在xid小鼠中诱导，但在nu/nu小鼠中不能诱导，表明T淋巴细胞依赖性的反应。B淋巴细胞激活剂脂多糖能够在nu/nu和正常小鼠中引起剧烈的类风湿因子产生，表明nu/nu小鼠含有能够产生应答的B细胞。在免疫复合物或LPS诱导的应答中产生的类风湿性关节炎抗体是Fc特异性的，并且对不与抗原结合的IgG具有相对低的亲和力。
Immunization of mice with a combination of passively administered syngeneic IgG (anti-p-azophenylarsonate [anti-Ars]) antibody and a soluble, multivalent form of the antibody''s corresponding antigen (Limulus polyphemus hemocyanin conjugated with Ars [Lph-Ars]) resulted in specific autoanti-IgG Fc (rheumatoid factor) production. The response was rapid and only anti-IgG of the IgM isotype is found. Because immunization with either the IgG antibody or the antigen alone did not result in rheumatoid antibody production, immune complexes appear to be the active form of the immunogens. Antibody/antigen ratios that resulted in maximal anti-IgG antibody responses were the same as those required for peak in vitro immunoprecipitation, i.e., equivalence. Previous exposure of the mice to the exogenously supplied antigen was not required for the response. The response to immune complexes is specific because mice immunized with IgG2a-containing complexes produced autoanti-IgG2a, while mice immunized with IgG1-containing complexes produced anti-IgG1 with little reactivity to other IgG isotypes. IgG2a blocked in its complement-fixing capacity was more effective in eliciting the anti-IgG2a response than native IgG2a, suggesting a possible role for the complement system in modulating the anti-IgG2a response. Induction of rheumatoid factor production by immune complexes could be induced in xid mice but not in nu/nu mice, indicating T lymphocyte dependence of the response. The B lymphocyte activator lipopolysaccharide was able to elicit vigorous rheumatoid factor production in both nu/nu and normal mice, demonstrating that nu/nu mice contain B cells capable of making the response. Rheumatoid antibody produced in the immune complex- or LPS-induced responses is Fc specific and has relatively low affinity for IgG that is not bound to antigen.