Modulation of single-cell IgG secretion frequency and rates in human memory B cells by CpG DNA, CD40L, IL-21, and cell division.
Modulation of single-cell IgG secretion frequency and rates in human memory B cells by CpG DNA, CD40L, IL-21, and cell division.
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DOI：
10.4049/jimmunol.0804233
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发表时间：
2009-09-01
期刊：
影响因子：
--
通讯作者：
Zand MS
中科院分区：
文献类型：
--
作者：
Henn AD;Rebhahn J;Brown MA;Murphy AJ;Coca MN;Hyrien O;Pellegrin T;Mosmann T;Zand MS
在CD27+Ig G类转换型人类记忆B细胞的召回反应中，分泌的总Ig G是Ig G分泌细胞(Ig G-SC)数量和各细胞分泌速率的函数。在这里，我们报告了定量ELISPOT方法(QELISPOT)，用于同时估计人类B细胞群体中单细胞免疫球蛋白分泌率和分泌细胞频率。我们发现CpG和细胞因子激活的CD27+IgMneg记忆B细胞的免疫球蛋白分泌速率具有很大的异质性，有两个主要的分泌速率亚群。B细胞受体的交联会降低具有高单位细胞免疫球蛋白分泌率的细胞的频率，同时CD27hi B细胞母细胞的频率也会降低。细胞死亡增加可能是BCR刺激的高比例的IgG-SC CD27hi B细胞母细胞减少的原因。相反，在CD40L+IL-4激活的人记忆B细胞中加入IL-21，可在B细胞中诱导出高比例的Ig G-SC群体，但每细胞的Ig G分泌率较低。人类B细胞免疫球蛋白分泌率的分布符合相同的双相分布和范围，而不受分裂级别的影响。这与CpG+Ck激活的B记忆B细胞群中不产生免疫球蛋白G的B细胞的存在一起，暗示着一种调节免疫球蛋白分泌的“开/关开关”。最后，这些数据支持一种混合的免疫球蛋白分泌模型，在该模型中，随着时间的推移，免疫球蛋白的分泌受到免疫球蛋白分泌细胞的频率及其免疫球蛋白分泌率的分布的调节。这是作者制作的手稿版本，接受在《免疫学杂志》(The JI)上发表。JI的出版商美国免疫学家协会(AAI)拥有这份手稿的版权。这一版本的手稿尚未由联合调查组复制或进行编辑校对；因此，它可能与联合调查组出版的最终版本(在线和印刷)不同。AAI(JI)对作者制作的本手稿版本或美国国立卫生研究院或任何其他第三方衍生的任何版本中的错误或遗漏不承担任何责任。记录的最终可引用版本可在www.jImmunol.org<；http://www.jimmunol.org>；上找到。
During the recall response by CD27+ IgG class switched human memory B cells, total IgG secreted is a function of the number of IgG secreting cells (IgG-SC) and the secretion rate of each cell. Here we report the quantitative ELISPOT method (qELISPOT) for simultaneous estimation of single cell IgG secretion rates and secreting cell frequencies in human B cell populations. We found that CD27+ IgMneg memory B cells activated with CpG and cytokines had considerable heterogeneity in the IgG secretion rates, with two major secretion rate subpopulations. B cell receptor cross-linking reduced the frequency of cells with high per-cell IgG secretion rates, with a parallel decrease in CD27hi B cell blasts. Increased cell death may account for the BCR-stimulated reduction in high-rate IgG-SC CD27hi B cell blasts. In contrast, the addition of IL-21 to CD40L +IL-4 activated human memory B cells induced a high-rate IgG-SC population in B cells with otherwise low per-cell IgG secretion rates. The profiles of human B cell IgG secretion rates followed the same biphasic distribution and range irrespective of division class. This, along with the presence of non-IgG-producing, dividing B cells in CpG+ck-activated B memory B cell populations, is suggestive of an “On/Off switch” regulating IgG secretion. Finally, these data support a mixture model of IgG secretion in which IgG secreted over time is modulated by the frequency of IgG secreting cells and the distribution of their IgG secretion rates. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org <http://www.jimmunol.org> .
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影响因子：
20.3
作者：
Huggins, Jennifer;Pellegrin, Tina;Zand, Martin S.
通讯作者：
Zand, Martin S.
影响因子：
2.2
作者：
CZERKINSKY, CC;NILSSON, LA;TARKOWSKI, A
通讯作者：
TARKOWSKI, A
影响因子：
2.9
作者：
Phillips, TM
通讯作者：
Phillips, TM
影响因子：
6.1
作者：
Rebhahn, Jonathan A.;Bishop, Courtney;Mosmann, Tim R.
通讯作者：
Mosmann, Tim R.
影响因子：
4.4
作者：
Good, Kim L.;Bryant, Vanessa L.;Tangye, Stuart G.
通讯作者：
Tangye, Stuart G.