Marcus H, David M, Canaan A, Kulova L, Lubin I, Segall H, Denes L, Erlich P, Galun E, Gan J
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Blood. 1995 Jul 1;86(1):398-406.
Lubin et al recently described a new approach that enables the generation of human/mouse chimera by adoptive transfer of human peripheral blood mononuclear cells (PBMC) into lethally irradiated normal strains of mice, radioprotected with bone marrow (BM) from donors with severe combined immune deficiency (SCID). In the present study, we demonstrate in such human/mouse chimera a marked humoral response to recall antigen, such as tetanus toxoid (TT) or hepatitis B surface antigen (HBsAg), as well as a significant primary response to keyhole limpet hemocyanin (KLH). Maximal anti-KLH response in human/Balb chimera was attained 2 to 4 weeks after the immunization and declined thereafter. One week after transplantation, the predominant anti-KLH subtype was IgM, while after 2 weeks, the dominance had shifted to IgG. Similar primary antibody response was also demonstrated against the human immunodeficiency virus (HIV) Nef protein. Comparison between human/Balb and human/SCID chimera showed a major difference in their ability to mount a primary response against KLH. In Balb/c recipients, more than half of the mice exhibited marked IgM titers against KLH, while there was hardly any anti-KLH IgM response in the SCID recipients. From the earliest time point onwards, when anti-KLH antibodies were found in the latter chimera, they were predominantly of the IgG type. We have previously shown that in human/Balb chimera, unlike in SCID recipients, dissemination of transplanted PBMC into the spleen and other internal organs occurs within 24 hours. Therefore, it is likely that the early seeding in the appropriate microenvironment of the lymphoid tissues, is crucial for the maintenance of virgin human B cells.
卢宾等人最近描述了一种新方法，该方法通过将人外周血单个核细胞（PBMC）过继转移到经致死剂量照射的正常小鼠品系中，并使用来自严重联合免疫缺陷（SCID）供体的骨髓（BM）进行辐射防护，从而能够生成人/小鼠嵌合体。在本研究中，我们在这种人/小鼠嵌合体中证明了对回忆抗原（如破伤风类毒素（TT）或乙型肝炎表面抗原（HBsAg））有显著的体液反应，以及对钥孔戚血蓝蛋白（KLH）有显著的初次反应。人/Balb嵌合体中抗KLH的最大反应在免疫后2至4周达到，此后下降。移植后1周，主要的抗KLH亚型是IgM，而2周后，优势已转移到IgG。针对人类免疫缺陷病毒（HIV）Nef蛋白也显示出类似的初次抗体反应。人/Balb和人/SCID嵌合体之间的比较显示，它们对KLH产生初次反应的能力存在重大差异。在Balb/c受体中，超过一半的小鼠表现出针对KLH的显著IgM滴度，而在SCID受体中几乎没有抗KLH IgM反应。从最早的时间点起，当在后一种嵌合体中发现抗KLH抗体时，它们主要是IgG类型。我们之前已经表明，在人/Balb嵌合体中，与SCID受体不同，移植的PBMC在24小时内就会扩散到脾脏和其他内部器官。因此，很可能在淋巴组织的适当微环境中早期播种对于维持未接触过抗原的人B细胞至关重要。
