论文标题

了解内存B细胞选择

Understanding Memory B Cell Selection

论文作者

Lindsly, Stephen, Gupta, Maya, Stansbury, Cooper, Rajapakse, Indika

论文摘要

哺乳动物的适应性免疫系统已经发展了数百万年,以成为对外国抗原的极有效防御。自适应免疫系统的体液反应会产生血浆B细胞和记忆B细胞,每个细胞都有自己的免疫目标。亲和力成熟过程被广泛视为解决抗原高亲和力的B细胞的全局优化问题的启发式方法。但是,记忆B细胞似乎是在亲和力成熟过程中有意选择的,并且具有较低的亲和力。我们建议,这种记忆B细胞选择过程可能是两个优化问题的近似解决方案:尽管突变或其他较小的差异,在将来对类似抗原的亲和力进行优化,并且在将来优化以使血浆B细胞的产生开始。考虑到数据表明某些B细胞突变比其他人更有可能,我们使用模拟为我们的假设提供证据。我们的发现与对突变抗原具有高亲和力的记忆B细胞一致,但没有提供强有力的证据表明,记忆B细胞将比选定的幼稚B细胞更有用,用于播种次生生发中心。

The mammalian adaptive immune system has evolved over millions of years to become an incredibly effective defense against foreign antigens. The adaptive immune system's humoral response creates plasma B cells and memory B cells, each with their own immunological objectives. The affinity maturation process is widely viewed as a heuristic to solve the global optimization problem of finding B cells with high affinity to the antigen. However, memory B cells appear to be purposely selected earlier in the affinity maturation process and have lower affinity. We propose that this memory B cell selection process may be an approximate solution to two optimization problems: optimizing for affinity to similar antigens in the future despite mutations or other minor differences, and optimizing to warm start the generation of plasma B cells in the future. We use simulations to provide evidence for our hypotheses, taking into account data showing that certain B cell mutations are more likely than others. Our findings are consistent with memory B cells having high-affinity to mutated antigens, but do not provide strong evidence that memory B cells will be more useful than selected naive B cells for seeding the secondary germinal centers.

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