CLONAL ANALYSIS OF LYMPHOCYTE-B RESPONSES TO PLASMODIUM-CHABAUDI INFECTION OF NORMAL AND IMMUNOPROTECTED MICE
CLONAL ANALYSIS OF LYMPHOCYTE-B RESPONSES TO PLASMODIUM-CHABAUDI INFECTION OF NORMAL AND IMMUNOPROTECTED MICE
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DOI：
10.1093/intimm/3.12.1207
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发表时间：
1991-12-01
影响因子：
4.4
通讯作者：
COUTINHO, A
中科院分区：
文献类型：
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作者：
LIMA, MRD;BANDEIRA, A;COUTINHO, A
寄生虫感染引起宿主免疫系统的显著紊乱，如高丙种球蛋白血症、自身免疫和免疫抑制所示，但关于感染过程中激活的B细胞克隆的数量、特异性和性能的信息很少。 我们已经解决了这些问题，在鼠疟疾模型中引起的疟原虫chabaudi，其中原发感染的结果在非常显着的B细胞反应，转移在IG同种型模式的免疫保护动物，免疫力可以转移到幼稚受体注射血清从晚期，但不是早期，感染。 我们已经量化了B细胞在两个不同的功能区室，即原始细胞和Ig分泌细胞感染，并比较正常的免疫动物。 我们还确定了克隆特异性的频率对几个自身抗原（DNA，肌球蛋白，转铁蛋白和红细胞），非自身蛋白或多糖抗原（KLH，莱万和葡聚糖），和寄生虫抗原在两个隔室，通过测量有限稀释分析和IG分泌ELISASPOT测定的母细胞反应性。 该实验设计使我们能够评估B细胞应答的特异性，比较这两种B细胞区室的克隆组成，并评估终末分化步骤中推定的特异性应答调节。 我们的研究结果表明，在这个特定的实验系统中：（i）初次感染时的B细胞反应是真正的非特异性反应，而免疫动物显示出更大的控制大量非特异性反应的能力;（ii）寄生虫特异性B细胞，特别是那些致力于产生IgG的细胞，在免疫个体中被选择性地刺激;（iii）自身反应性B细胞不被选择性地刺激，但是增加的自身抗体产生可能是由于在各个克隆中对终末分化的控制的扰动;（iv）对某些非自身抗原（例如KLH和葡聚糖）具有特异性的克隆被选择性地接合和调节，这可能与感染后的免疫抑制有关。
Parasite infection causes marked perturbations in the host immune system, as shown by hypergammaglobulinemia, autoimmunity and immune depression, but there is little information on the number, specificities and performance of B cell clones activated in the course of infection. We have addressed these questions in a model of murine malaria induced by Plasmodium chabaudi, where primary infection results in very marked B cell responses that shift in Ig isotype pattern in immunoprotected animals, and where immunity can be transferred to naive recipients by injection of serum from late, but not early, infection. We have quantitated B cells responding to infection in two distinct functional compartments, namely blast cells and Ig-secreting cells, and compared normal with immune animals. We have also determined the frequencies of clonal specificities towards several autoantigens (DNA, myosin, transferrin and red cells), non-self protein or polysaccharide antigens (KLH, levan and dextran), and parasite antigens in both compartments, by measuring blast cell reactivities in limiting dilution analyses and Ig secretion in ELISASPOT assays. This experimental design allowed us to assess the specificity of the B cell responses, to compare the clonal composition of these two B cell compartments, and to evaluate putative specific response regulation at the step of terminal differentiation. Our results show that, in this particular experimental system: (i) B cell responses in primary infection are truly non-specific while immune animals show a greater ability to control the massive non-specific response; (ii) parasite specific B cells, particularly those committed to IgG production, are selectively stimulated in immune individuals; (iii) autoreactive B cells are not selectively stimulated, but increased autoantibody production may result from perturbation in the control of terminal differentiation in the respective clones; (iv) clones with specificity to some non-self antigens (e.g. KLH and dextran) are selectively engaged and regulated, which might have implications for the immunosuppression following infection.