Evidence for selection of a population of multi-reactive B cells into the splenic marginal zone
Evidence for selection of a population of multi-reactive B cells into the splenic marginal zone
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DOI：
10.1093/intimm/9.1.27
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发表时间：
1997-01-01
影响因子：
4.4
通讯作者：
Kearney, JF
中科院分区：
文献类型：
--
作者：
Chen, XJ;Martin, F;Kearney, JF
抗体对自身抗原的反应性是免疫系统的正常组成部分。为了研究自身反应性B细胞产生和维持的机制，我们分析了转基因小鼠中的B细胞发育，所述转基因小鼠表达来自免疫前库的重排的V（H）81 X重链。在这些小鼠中，>95%的B细胞表达与多种κ轻链相关的转基因，但V（κ）1C是优势轻链，这些具有相同V（kappa）1C-J（kappa）5连接的转基因B细胞在体内通常不分泌IgM，但是通过体外LPS活化或在杂交瘤永生化后，衍生自这些α细胞的抗体是自身反应性的，并且识别来自不同组织的胞质内蛋白上的普遍存在的表位。它们具有长寿的边缘区A细胞的表型和定位模式，并且它们在体内的发育被注射可溶性V（H）81 X-V（kappa）1CJ（kappa）5 IgM抗体阻断。在该转基因小鼠中的观察为自身反应性B细胞群体的正选择提供了证据。这些B细胞进入a细胞的外周池，在那里它们定位于脾的边缘区，并且与其他转基因表达B细胞相反，不分泌IgM抗体。
Antibody reactivity to self-antigens is a normal component of the immune system. To study the mechanism by which self-reactive B cells are generated and maintained, we analyzed B cell development in transgenic mice that express a rearranged V(H)81X heavy chain from the preimmune repertoire, In these mice, >95% of B cells express the transgene in association with a variety of kappa light chains but V(kappa)1C being the dominant light chain, These transgenic B cells with identical V(kappa)1C-J(kappa)5 joins do not normally secrete IgM in vivo, but antibodies derived from these a cells, through LPS activation in vitro or after hybridoma immortalization, are self-reactive and recognize an ubiquitous epitope(s) on intracytoplasmic proteins from different tissues. They have the phenotype and localization pattern of long-lived marginal zone a cells and their development in vivo is blocked by injection of soluble V(H)81X-V(kappa)1CJ(kappa)5 IgM antibody, The observations in this transgenic mouse provide evidence for positive selection of a population of self-reactive B cells. These B cells enter the peripheral pool of a cells where they localize in the marginal zone of the spleen and, in contrast to other transgene-expressing B cells, do not secrete IgM antibody.