Lima M R, Bandeira A, Falanga P, Freitas A A, Kipnis T L, da Silva L P, Coutinho A
Unité d'Immunobiologie, Institut Pasteur, Paris, France.
Int Immunol. 1991 Dec;3(12):1207-16. doi: 10.1093/intimm/3.12.1207.
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.
寄生虫感染会导致宿主免疫系统出现显著紊乱，如高球蛋白血症、自身免疫和免疫抑制等，但关于感染过程中被激活的B细胞克隆的数量、特异性和功能，目前所知甚少。我们在由查巴迪疟原虫诱导的小鼠疟疾模型中研究了这些问题，在该模型中，初次感染会引发非常显著的B细胞反应，在获得免疫保护的动物中，Ig同种型模式会发生变化，并且通过注射感染后期而非早期的血清，可以将免疫力转移给未感染的受体。我们对两个不同功能区室中对感染产生反应的B细胞进行了定量，即母细胞和分泌Ig的细胞，并将正常动物与免疫动物进行了比较。我们还通过在有限稀释分析中测量母细胞反应性以及在ELISASPOT试验中测量Ig分泌，确定了这两个区室中针对几种自身抗原（DNA、肌球蛋白、转铁蛋白和红细胞）、非自身蛋白质或多糖抗原（钥孔戚血蓝蛋白、果聚糖和葡聚糖）以及寄生虫抗原的克隆特异性频率。这种实验设计使我们能够评估B细胞反应的特异性，比较这两个B细胞区室的克隆组成，并在终末分化步骤评估假定的特异性反应调节。我们的结果表明，在这个特定的实验系统中：（i）初次感染时的B细胞反应是真正非特异性的，而免疫动物表现出更强的能力来控制大量的非特异性反应；（ii）寄生虫特异性B细胞，特别是那些产生IgG的B细胞，在免疫个体中被选择性刺激；（iii）自身反应性B细胞没有被选择性刺激，但自身抗体产生增加可能是由于各个克隆终末分化控制受到干扰所致；（iv）对某些非自身抗原（如钥孔戚血蓝蛋白和葡聚糖）具有特异性的克隆被选择性激活和调节，这可能与感染后的免疫抑制有关。
