Antigen Receptor Specificity and Cell Location Influence the Diversification and Selection of the B-1a Cell Pool with Age.
Antigen Receptor Specificity and Cell Location Influence the Diversification and Selection of the B-1a Cell Pool with Age.
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DOI：
10.4049/jimmunol.1901302
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发表时间：
2020-08-01
期刊：
影响因子：
--
通讯作者：
Holodick NE
中科院分区：
文献类型：
--
作者：
Tsuji N;Rothstein TL;Holodick NE
B-1a细胞通过产生天然免疫球蛋白提供立即和必要的感染保护，由于最小的N-区插入，天然免疫球蛋白是种系样的。我们之前已经证明，由于选择的结果，腹膜B-1a细胞衍生的磷酸胆碱（PC）特异性和总IgM随着年龄的增长而远离种系（N-添加的增加证明了这一点）。在年轻的小鼠中，抗磷脂酰胆碱（PtC）抗体，如抗PC抗体，含有很少的N-添加，并已被证明是必不可少的保护细菌败血症。在此，我们证明PtC特异性腹膜B-1a细胞IgM的种系样状态不随年龄而变化。与此形成直接对比的是，脾PtC结合B-1a细胞群在老年人中不保持其IgM种系状态。此外，脾PtC结合B-1a细胞显示更多样化的VH使用在年轻和老年人相比，腹膜PtC结合B-1a细胞。虽然腹膜PtC结合群体随着年龄的增长而增加VH 12的使用，但我们观察到腹膜和脾脏PtC+群体之间VH 11，VH 12和VH 2的差异使用。这些结果表明，随着年龄的增长，不同的选择压力发生在B-1a细胞在不同的位置表达不同的特异性。总体而言，这些结果阐明了进一步阐明B-1a细胞在产生和选择方面如何随着时间的推移而受到影响的必要性，这两者都有助于随着年龄的增长而产生实际和可用的天然IgM库。这些研究将有助于为老年人制定更有效的疫苗接种和治疗策略。
B-1a cells provide immediate and essential protection from infection through production of natural immunoglobulin, which is germline-like due to minimal insertion of N-region additions. We have previously demonstrated peritoneal B-1a cell derived phosphorylcholine (PC)-specific and total IgM moves away from germline (as evidenced by an increase in N-additions) with age as a result of selection. In young mice, anti-phosphatidylcholine (PtC) antibodies, like anti-PC antibodies, contain few N-additions, and have been shown to be essential in protection from bacterial sepsis. Herein, we demonstrate the germline-like status of PtC specific peritoneal B-1a cell IgM does not change with age. In direct contrast, the splenic PtC-binding B-1a cell population does not preserve its IgM germline status in the aged. Furthermore, splenic PtC-binding B-1a cells displayed more diverse VH use in both the young and aged as compared to peritoneal PtC-binding B-1a cells. While the peritoneal PtC-binding population increased VH12 use with age, we observed differential use of VH11, VH12, and VH2 between the peritoneal and splenic PtC+ populations with age. These results suggest disparate selection pressures occur with age upon B-1a cells expressing different specificities in distinct locations. Overall, these results illuminate the need to further elucidate how B-1a cells are influenced over time in terms of production and selection, both of which contribute to the actual and available natural IgM repertoire with increasing age. Such studies would aid in the development of more effective vaccination and therapeutic strategies in the aged population.
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影响因子：
11.4
作者：
GU, H;FORSTER, I;RAJEWSKY, K
通讯作者：
RAJEWSKY, K
DOI：
10.1084/jem.172.5.1377
发表时间：
1990-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Feeney AJ
通讯作者：
Feeney AJ
影响因子：
15.3
作者：
Baumgarth, N;Herman, O C;Jager, G C;Brown, L E;Herzenberg, L A;Chen, J
通讯作者：
Chen, J
影响因子：
5.4
作者：
Holodick, Nichol E.;Repetny, Karen;Zhong, Xuemei;Rothstein, Thomas L.
通讯作者：
Rothstein, Thomas L.
影响因子：
4.4
作者：
Chumley, MJ;Dal Porto, JM;Cambier, JC
通讯作者：
Cambier, JC