Bray K R, Gershwin M E, Skelly R R, Ahmed A, Kincade P W
J Immunol. 1984 Jun;132(6):2913-8.
The mechanism of polyclonal expansion of B cells and subsequent autoantibody production in New Zealand mice remains a critical question. We have been studying the requirements for autoantibody production both in NZB mice as well as NZB mice congenic with the Xid gene of CBA/N mice. In this study, we have attempted to alter the immunologic phenotype of NZB.Xid mice by transfer of cells from young and old NZB mice. There was little difficulty in restoring normal levels of serum IgM, IgG3, splenic Lyb-5 cells, and response to DNP-Ficoll in young NZB.Xid mice that were injected with young NZB bone marrow cells. Although such animals had an almost immediate change in their immune profile to values characteristic of NZB mice, they required, much like unmanipulated NZB mice, a latency period of an additional 6 mo before autoantibodies were detected. In contrast, adult NZB.Xid mice, who likewise developed an immune profile similar to NZB after transfer of bone marrow cells from young NZB mice, began to express autoantibodies immediately without any latency period. NZB.Xid mice who were recipients of adult NZB bone marrow cells did not show sustained autoantibody production, reflecting the limited state of B cell precursors in adult NZB mice. Thus, the age of both donor cells and the age of recipient mice are critical factors for determining the latency period and the age at which autoantibodies will appear. Similarly we attempted to alter the production of autoantibodies in NZB mice that were irradiated and injected with bone marrow cells from NZB.Xid animals. NZB mice had a major amelioration of disease when they received cell transfers from young NZB.Xid mice. This amelioration, which included the acquisition of the immune profile of NZB.Xid animals, was not seen in adult NZB mice that were recipient of young NZB cells. We suggest that although Lyb-5 cells may be the effective mechanism for autoantibody production, there are other interacting influences that may selectively turn on or turn off autoantibodies and that are required and are responsible for the latency period.
新西兰小鼠中B细胞多克隆扩增及随后自身抗体产生的机制仍是一个关键问题。我们一直在研究NZB小鼠以及与CBA/N小鼠Xid基因同源的NZB小鼠产生自身抗体的条件。在本研究中，我们试图通过移植来自年轻和年老NZB小鼠的细胞来改变NZB.Xid小鼠的免疫表型。给年轻的NZB.Xid小鼠注射年轻NZB骨髓细胞后，恢复血清IgM、IgG3、脾Lyb-5细胞的正常水平以及对DNP-菲可的反应几乎没有困难。尽管这类动物的免疫谱几乎立即改变为NZB小鼠的特征值，但它们与未处理的NZB小鼠一样，在检测到自身抗体之前还需要额外6个月的潜伏期。相比之下，成年NZB.Xid小鼠在移植来自年轻NZB小鼠的骨髓细胞后，同样形成了类似于NZB的免疫谱，它们立即开始表达自身抗体，没有任何潜伏期。接受成年NZB骨髓细胞的NZB.Xid小鼠没有表现出持续的自身抗体产生，这反映了成年NZB小鼠中B细胞前体的有限状态。因此，供体细胞的年龄和受体小鼠的年龄都是决定潜伏期以及自身抗体出现年龄的关键因素。同样，我们试图改变经照射并注射来自NZB.Xid动物骨髓细胞的NZB小鼠中自身抗体的产生。当NZB小鼠接受来自年轻NZB.Xid小鼠的细胞移植时，疾病有了显著改善。这种改善包括获得NZB.Xid动物的免疫谱，而在接受年轻NZB细胞的成年NZB小鼠中没有观察到这种改善。我们认为，尽管Lyb-5细胞可能是产生自身抗体的有效机制，但还有其他相互作用的影响因素，可能会选择性地开启或关闭自身抗体，并且这些因素是潜伏期所必需的且与之相关。
