Kenny J J, Rezanka L J, Lustig A, Fischer R T, Yoder J, Marshall S, Longo D L
Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
J Immunol. 2000 Apr 15;164(8):4111-9. doi: 10.4049/jimmunol.164.8.4111.
IgH and L chain transgenes encoding a phosphocholine (PC)-specific Ig receptor were introduced into recombinase-activating gene (Rag-2-/-) knockout mice. The PC-specific B cells that developed behaved like known autoreactive lymphocytes. They were 1) developmentally arrested in the bone marrow, 2) unable to secrete Ab, 3) able to escape clonal deletion and develop into B1 B cells in the peritoneal cavity, and 4) rescued by overexpression of bcl-2. A second IgL chain was genetically introduced into Rag-2-/- knockout mice expressing the autoreactive PC-specific Ig receptor. These dual L chain-expressing mice had B cells in peripheral lymphoid organs that coexpressed both anti-PC Ab as well as Ab employing the second available L chain that does not generate an autoreactive PC-specific receptor. Coexpression of the additional Ig molecules rescued the autoreactive anti-PC B cells and relieved the functional anergy of the anti-PC-specific B cells, as demonstrated by detection of circulating autoreactive anti-PC-Abs. We call this novel mechanism by which autoreactive B cells can persist by compromising allelic exclusion receptor dilution. Rescue of autoreactive PC-specific B cells would be beneficial to the host because these Abs are vital for protection against pathogens such as Streptococcus pneumoniae.
将编码磷酸胆碱（PC）特异性Ig受体的IgH和L链转基因导入重组激活基因（Rag-2-/-）敲除小鼠。发育形成的PC特异性B细胞表现得如同已知的自身反应性淋巴细胞。它们：1）在骨髓中发育停滞；2）无法分泌抗体；3）能够逃避克隆清除并在腹腔中发育为B1 B细胞；4）通过bcl-2的过表达而得到拯救。将第二条IgL链基因导入表达自身反应性PC特异性Ig受体的Rag-2-/-敲除小鼠。这些表达双L链的小鼠在外周淋巴器官中有B细胞，这些B细胞共表达抗PC抗体以及使用第二条可用L链的抗体，该L链不会产生自身反应性PC特异性受体。额外Ig分子的共表达拯救了自身反应性抗PC B细胞，并缓解了抗PC特异性B细胞的功能无反应性，循环中的自身反应性抗PC抗体的检测证明了这一点。我们将这种自身反应性B细胞通过损害等位基因排斥受体稀释而得以持续存在的新机制称为受体稀释。自身反应性PC特异性B细胞的拯救对宿主有益，因为这些抗体对于抵御诸如肺炎链球菌等病原体至关重要。
