Imprinting the fate of antigen-reactive B cells through the affinity of the B cell receptor
Imprinting the fate of antigen-reactive B cells through the affinity of the B cell receptor
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DOI：
10.4049/jimmunol.177.11.7723
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发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Erickson, Loren D.
中科院分区：
文献类型：
--
作者：
O'Connor, Brian P.;Vogel, Laura A.;Erickson, Loren D.
长寿的浆细胞（PC）和记忆B细胞（B-B细胞）构成持久的体液免疫的细胞组分，而快速产生IG的短命的PC对应于宿主的需要，立即保护免受病原体。在这项研究中，我们表明，先天亲和力的BCR的Ag印记后，幼稚B细胞的分化命运，成为短或长寿命的PC和B-BCRs。使用BCR转基因小鼠与不同的亲和力的Ag，幼稚B细胞与高亲和力失去了他们的能力，形成生发中心（GC），既不开发B-BCRs也不长寿命的PC，注定要一个短寿命的PC的命运。中等亲和力的相互作用导致加速GC反应，并分化为长寿的PC，但B-β仍然灭绝。相比之下，较低的亲和力相互作用显示出缓和的GC，产生B-β和亲和力成熟的长寿命PC。因此，存在由固有BCR亲和力控制的从初级到综合体液免疫应答的连续体。
Long-lived plasma cells (PCs) and memory B cells (B-mem) constitute the cellular components of enduring humoral immunity, whereas short-lived PCs that rapidly produce Ig correspond to the host's need for immediate protection against pathogens. In this study we show that the innate affinity of the BCR for Ag imprints upon naive B cells their differentiation fate to become short-or long-lived PCs and B-mem. Using BCR transgenic mice with varying affinities for Ag, naive B cells with high affinity lose their capacity to form germinal centers (GCs), develop neither B-mem nor long-lived PCs, and are destined to a short-lived PC fate. Moderate affinity interactions result in hastened GC responses, and differentiation to long-lived PCs, but B-mem remain extinct. In contrast, lower affinity interactions show tempered GCs, producing B-mem and affinity-matured, long-lived PCs. Thus, a continuum of elementary to comprehensive humoral immune responses exists that is controlled by inherent BCR affinity.