Aging is known to induce immunosenescence, resulting in alterations in both the innate and adaptive immune system. Here we evaluated the effects of aging on B cell subsets in peripheral blood of 155 immunologically healthy individuals in four age categories (range 20-95y) via multi-parameter flow cytometry. Furthermore, we studied the naive and antigen-experienced B cell receptor (BCR) repertoire of different age groups and compared it to the clonal BCR repertoire of chronic lymphocytic leukemia (CLL), a disease typically presenting in elderly individuals. Total numbers and relative frequencies of B cells were found to decline upon aging, with reductions in transitional B cells, memory cell types, and plasma blasts in the 70 + y group. The BCR repertoire of naive mature B cells and antigen-experienced B cells did not clearly alter until age 70y. Clear changes in IGHV gene usage were observed in naive mature B cells of 70 + y individuals, with a transitional pattern in the 50-70y group. IGHV gene usage of naive mature B cells of the 50-70y, but not the 70 + y, age group resembled that of both younger (50-70y) and older (70 + y) CLL patients. Additionally, CLL-associated stereotypic BCR were found as part of the healthy control BCR repertoire, with an age-associated increase in frequency of several stereotypic BCR (particularly subsets #2 and #5). Composition of the peripheral B cell compartment changes with ageing, with clear reductions in non-switched and CD27 + IgG+ switched memory B cells and plasma blasts in especially the 70 + y group. The BCR repertoire is relatively stable until 70y, whereafter differences in IGHV gene usage are seen. Upon ageing, an increasing trend in the occurrence of particular CLL-associated stereotypic BCR is observed.

中文翻译：

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来自健康个体的正常 BCR 库中 CLL 相关的刻板 B 细胞受体的存在随着年龄的增长而增加

众所周知，衰老会诱导免疫衰老，从而导致先天性和适应性免疫系统的改变。在这里，我们通过多参数流式细胞术评估了衰老对四个年龄组（范围 20-95 岁）的 155 名免疫健康个体外周血 B 细胞亚群的影响。此外，我们研究了不同年龄组的幼稚和抗原经历的 B 细胞受体 (BCR) 库，并将其与慢性淋巴细胞白血病 (CLL) 的克隆 BCR 库进行了比较，慢性淋巴细胞白血病 (CLL) 是一种通常出现在老年人中的疾病。发现 B 细胞的总数和相对频率随着年龄的增长而下降，70 + y 组的过渡 B 细胞、记忆细胞类型和浆母细胞减少。幼稚成熟 B 细胞和经历过抗原的 B 细胞的 BCR 库直到 70 岁才明显改变。在 70 + y 个体的幼稚成熟 B 细胞中观察到 IGHV 基因使用的明显变化，在 50-70 y 组中具有过渡模式。50-70 岁但不是 70 + y 年龄组的幼稚成熟 B 细胞的 IGHV 基因使用类似于年轻 (50-70 岁) 和老年 (70 + y) CLL 患者。此外，CLL 相关的刻板印象 BCR 被发现是健康对照 BCR 曲目的一部分，几个刻板印象 BCR（特别是子集#2 和#5）的频率随年龄增加而增加。外周 B 细胞区室的组成随着年龄的增长而变化，尤其是 70 + y 组中的非转换和 CD27 + IgG+ 转换的记忆 B 细胞和浆母细胞明显减少。BCR 库在 70 年前相对稳定，此后看到 IGHV 基因使用的差异。随着年龄的增长，