Idiotype vaccination against murine B cell lymphoma. Humoral and cellular responses elicited by tumor-derived immunoglobulin M and its molecular subunits.
Idiotype vaccination against murine B cell lymphoma. Humoral and cellular responses elicited by tumor-derived immunoglobulin M and its molecular subunits.
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DOI：
10.4049/jimmunol.139.8.2825
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发表时间：
1987-10
影响因子：
4.4
通讯作者：
Michael J. Campbell;William L. Carroll;Shinichiro Kon;Kristiaan Thielemans;Jonathan B. Rothbard;S. Levy-S.
中科院分区：
文献类型：
--
作者：
Michael J. Campbell;William L. Carroll;Shinichiro Kon;Kristiaan Thielemans;Jonathan B. Rothbard;S. Levy-S.
使用来自同源 38C13 淋巴瘤的独特型免疫球蛋白 M (IgM) 及其分子亚基对 C3H/HeN 小鼠进行免疫。使用独特型 IgM (38C-Id) 进行免疫可产生独特型特异性体液和细胞免疫，并可防止致命的肿瘤细胞攻击。通过电洗脱从制备型聚丙烯酰胺凝胶中分离重链 (H38C) 和轻链 (L38C)。这两种免疫原都诱导了对随后的肿瘤攻击的显着抵抗力。通过将重链和轻链可变区基因克隆到表达质粒pATH-11中获得trpE融合蛋白形式的可变区免疫原。其中，只有 trpE-VH38C 免疫原对肿瘤攻击产生了免疫抵抗力。最后，确定了38C-Id轻链的核酸序列，并根据相应的氨基酸序列和预测的二级结构分析，选择互补决定区3中具有潜在抗原性的区域用于生产合成肽。使用这种合成肽进行疫苗接种可显着抑制肿瘤生长。对这些疫苗产生的体液和细胞免疫的分析表明，仅在 38C-Id、H38C 和 trpE-VH38C 免疫血清中存在与天然独特型 IgM 反应的抗体，尽管后两者不是独特型特异性的。在所有免疫动物中均观察到独特型特异性淋巴细胞，其响应天然 38C-Id 而增殖。除融合蛋白免疫原外，需要与免疫原性载体蛋白（匙孔血蓝蛋白或甲状腺球蛋白）缀合才能获得最佳的体液和细胞反应。
C3H/HeN mice were immunized with idiotypic immunoglobulin M (IgM) and its molecular subunits from the syngeneic 38C13 lymphoma. Immunization with idiotypic IgM (38C-Id) resulted in idiotype-specific humoral and cellular immunity and protection against a lethal tumor cell challenge. Heavy (H38C) and light (L38C) chains were isolated by electroelution from preparative polyacrylamide gels. Both of these immunogens induced significant resistance to a subsequent tumor challenge. Variable region immunogens, in the form of trpE-fusion proteins, were obtained by cloning heavy and light chain variable region genes into the expression plasmid pATH-11. Of these, only the trpE-VH38C immunogen yielded immune resistance to tumor challenge. Finally, the nucleic acid sequence of 38C-Id light chain was determined and, based on the corresponding amino acid sequence and an analysis of predicted secondary structure, a region of potential antigenicity in complementarity-determining region 3 was chosen for the production of a synthetic peptide. Vaccination with this synthetic peptide resulted in significant suppression of tumor growth. Analysis of the humoral and cellular immunity generated by these vaccines revealed the presence of antibodies reactive with native idiotypic IgM only in 38C-Id, H38C, and trpE-VH38C immune sera, although the latter two were not idiotype-specific. Idiotype-specific lymphocytes, which proliferated in response to native 38C-Id, were observed in all immune animals. With the exception of the fusion protein immunogens, conjugation to an immunogenic carrier protein (keyhole limpet hemocyanin or thyroglobulin) was required for optimal humoral and cellular responses.