Memory B-cell persistence is independent of persisting immunizing antigen

Memory B-cell persistence is independent of persisting immunizing antigen
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DOI:
10.1038/35036600
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发表时间:
2000-10-05
期刊:
影响因子:
64.8
通讯作者:
Rajewsky, K
Rajewsky, K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Maruyama, M;Lam, KP;Rajewsky, K

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抗体系统中的免疫记忆是在T细胞依赖的反应中产生的,并由长寿记忆B细胞携带,后者通过高亲和力抗体识别抗原(1,2)。但仍然存在争议:(1)这些B细胞是否代表真正的“记忆”细胞(即它们的维持独立于免疫抗原),或者它们是否是免疫抗原驱动的慢性免疫反应的产物,免疫抗原可以在机体内特殊的抗原呈递细胞(滤泡树突状细胞)表面保留较长时间(3)。细胞转移实验提供了支持免疫抗原(4,5)作用的证据;然而,对完整动物的记忆细胞的分析表明,这些细胞大多处于休息状态(6),在缺乏可检测到的T细胞帮助(7)或滤泡树突状细胞(8)的情况下可以持续存在。在这里,我们表明,通过使用Cre重组酶介导的遗传开关,记忆B细胞确实可以在动物体内长期保持其抗体特异性,类似于保留其原始抗原结合特异性的细胞。
Immunological memory in the antibody system is generated in T-cell-dependent responses and carried by long-lived memory B cells that recognize antigen by high-affinity antibodies(1,2). But it remains controversial(1) whether these B cells represent true 'memory' cells (that is, their maintenance is independent of the immunizing antigen), or whether they are a product of a chronic immune response driven by the immunizing antigen, which can be retained in the organism for extended time periods on the surface of specialized antigen-presenting cells (follicular dendritic cells)(3). Cell transfer experiments provided evidence in favour of a role of the immunizing antigen(4,5); however, analysis of memory cells in intact animals, which showed that these cells are mostly resting(6) and can persist in the absence of detectable T-cell help(7) or follicular dendritic cells(8), argued against it. Here we show, by using a genetic switch mediated by Cre recombinase, that memory B cells switching their antibody specificity away from the immunizing antigen are indeed maintained in the animal over long periods of time, similar to cells retaining their original antigen-binding specificity.