Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion.
Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion.
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DOI：
10.1084/jem.20060964
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发表时间：
2007-03-19
期刊：
影响因子：
--
通讯作者：
van Dongen JJ
中科院分区：
文献类型：
--
作者：
van Zelm MC;Szczepanski T;van der Burg M;van Dongen JJ
增殖对B淋巴细胞动态平衡和抗原反应的贡献在很大程度上是未知的。我们通过计算IGK删除重排的Kappa删除重组切除环(KREC)上基因组编码关节和信号关节之间的比率来量化小鼠和人类B淋巴细胞亚群的复制历史。这一方法得到了体外增殖研究的验证。我们证明，幼稚的成熟B淋巴细胞，而不是过渡性B淋巴细胞，在外周没有体细胞突变的情况下，在体内进行动态平衡增殖。依赖T细胞的B细胞的增殖显著高于非T细胞依赖的B细胞，体细胞超突变的频率高于非T细胞依赖的反应，这与T细胞依赖的抗体反应的健壮性和高亲和力相吻合。与儿童相比，成人中经历过抗原的B淋巴细胞有更广泛的增殖和体细胞高突变，这表明对额外的抗原暴露有连续的反应。我们的联合观察揭示了增殖对B淋巴细胞动态平衡和抗原诱导的B细胞增殖的贡献。我们提出了这两个过程在体液免疫中的重要作用。这些新的见解将支持对造血干细胞移植或B细胞定向抗体治疗后外周B细胞再生的理解，以及对常见变量免疫缺陷或其他抗体缺陷患者体内稳态或抗原诱导的B细胞增殖缺陷的识别。
The contribution of proliferation to B lymphocyte homeostasis and antigen responses is largely unknown. We quantified the replication history of mouse and human B lymphocyte subsets by calculating the ratio between genomic coding joints and signal joints on kappa-deleting recombination excision circles (KREC) of the IGK-deleting rearrangement. This approach was validated with in vitro proliferation studies. We demonstrate that naive mature B lymphocytes, but not transitional B lymphocytes, undergo in vivo homeostatic proliferation in the absence of somatic mutations in the periphery. T cell–dependent B cell proliferation was substantially higher and showed higher frequencies of somatic hypermutation than T cell–independent responses, fitting with the robustness and high affinity of T cell–dependent antibody responses. More extensive proliferation and somatic hypermutation in antigen-experienced B lymphocytes from human adults compared to children indicated consecutive responses upon additional antigen exposures. Our combined observations unravel the contribution of proliferation to both B lymphocyte homeostasis and antigen-induced B cell expansion. We propose an important role for both processes in humoral immunity. These new insights will support the understanding of peripheral B cell regeneration after hematopoietic stem cell transplantation or B cell–directed antibody therapy, and the identification of defects in homeostatic or antigen-induced B cell proliferation in patients with common variable immunodeficiency or another antibody deficiency.
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在体外和体内成熟B细胞中Lambda轻链基因的重排。重新表达重组激活基因（RAG）产品的功能。
影响因子：
15.3
作者：
Hikida, M;Ohmori, H
通讯作者：
Ohmori, H
DOI：
10.1073/pnas.96.4.1536
发表时间：
1999-02-16
影响因子：
11.1
作者：
Kong, FK;Chen, CLH;Cooper, MD
通讯作者：
Cooper, MD
DOI：
10.1084/jem.194.8.1151
发表时间：
2001-10-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hao Z;Rajewsky K
通讯作者：
Rajewsky K
影响因子：
4.4
作者：
Cabatingan, MS;Schmidt, MR;Woodland, RT
通讯作者：
Woodland, RT
影响因子：
4.4
作者：
Jamieson, AM;Isnard, P;Raulet, DH
通讯作者：
Raulet, DH