Sekiguchi Debora R, Yunk Lenka, Gary David, Charan Deepshikha, Srivastava Bhaskar, Allman David, Weigert Martin G, Prak Eline T Luning
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.
J Immunol. 2006 Jun 1;176(11):6879-87. doi: 10.4049/jimmunol.176.11.6879.
Tolerance to dsDNA is broken in mice with a high-affinity anti-DNA H chain transgene, 56R, on the C57BL/6 background (B6.56R). B6.56R produce more anti-dsDNA Abs than BALBc.56R. To investigate how anti-DNA Abs are regulated on the B6 background, phenotypic and genetic studies were performed. B6.56R have reduced numbers of B cells and phenotypically altered B cell subsets, including relative increases in the proportions of IgM-negative bone marrow B cells, cells with a marginal zone phenotype, and cells with a transitional T3 phenotype. The peripheral B cell repertoire in B6.56R is restricted: most B cells express the 56R H chain and use a similar, limited subset of editor L chains. DNA binding is more common in B6.56R because the repertoire is shifted toward L chains that are more permissive for DNA binding. H chain editing is also observed and is increased in spontaneous as compared with LPS hybridomas. A subset of spontaneous hybridomas appears to lack H chain expression.
在C57BL/6背景（B6.56R）下带有高亲和力抗DNA重链转基因56R的小鼠中，对双链DNA的耐受性被打破。B6.56R产生的抗双链DNA抗体比BALBc.56R更多。为了研究在B6背景下抗DNA抗体是如何被调节的，进行了表型和遗传学研究。B6.56R的B细胞数量减少，并且B细胞亚群的表型发生改变，包括IgM阴性骨髓B细胞、具有边缘区表型的细胞以及具有过渡性T3表型的细胞比例相对增加。B6.56R的外周B细胞库受到限制：大多数B细胞表达56R重链，并使用相似的、有限的一组编辑轻链。DNA结合在B6.56R中更常见，因为库向对DNA结合更宽容的轻链转移。还观察到重链编辑，并且与LPS杂交瘤相比，自发杂交瘤中的重链编辑增加。一部分自发杂交瘤似乎缺乏重链表达。
