Homeostatic 'bystander' proliferation of human peripheral blood B cells in response to polyclonal T-cell stimulation in vitro
Homeostatic 'bystander' proliferation of human peripheral blood B cells in response to polyclonal T-cell stimulation in vitro
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DOI：
10.1093/intimm/dxv032
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发表时间：
2015-11-01
影响因子：
4.4
通讯作者：
Witkowski, Jacek M.
中科院分区：
文献类型：
--
作者：
Jasiulewicz, Aleksandra;Lisowska, Katarzyna A.;Witkowski, Jacek M.
在缺乏抗原(再)刺激的情况下，维持足够数量的B淋巴细胞和免疫球蛋白保护性水平的机制仍不完全清楚。同时，我们的结果表明，在抗CD3或刀豆蛋白A(ConA)刺激的健康人外周血单个核细胞体外培养5天后，幼稚B细胞和记忆B细胞都能被强烈和非特异性地激活(以丝裂原样方式)。这种多克隆、旁观者的B细胞激活包括大多数B细胞的多个分裂(在此通过分裂细胞跟踪的流式细胞仪技术进行评估)和显著的抗体[免疫球蛋白M(IgM)和免疫球蛋白G]分泌。观察到的CD19(+)B细胞的增殖依赖于与刺激的T辅助(T-h)细胞的接触(通过CD40-CD40L相互作用)和B细胞对分泌IL-5、IL-10和IL-4的反应，并与这些T-h衍生分子的水平相关，而不涉及BCR/CD19复合体的连接。我们认为，这种效应可能反映了体内发生的情况，即未受刺激的外周B淋巴细胞的动态平衡增殖，为应对任何新的(或同源)抗原挑战提供了一个随时准备好的高效抗体产生池。
The mechanisms of maintenance of adequate numbers of B lymphocytes and of protective levels of immunoglobulins in the absence of antigenic (re) stimulation remain not fully understood. Meanwhile, our results presented here show that both peripheral blood naive and memory B cells can be activated strongly and non-specifically (in a mitogen-like fashion) in 5-day in vitro cultures of anti-CD3-or concanavalin A (Con A)-stimulated peripheral blood mononuclear cells of healthy people. This polyclonal, bystander activation of the B cells includes multiple divisions of most of them (assessed here by the flow cytometric technique of dividing cell tracking) and significant antibody [immunoglobulin M (IgM) and IgG] secretion. Observed proliferation of the CD19(+) B cells depends on contact with stimulated T helper (T-h) cells (via CD40-CD40L interaction) and on the response of B cells to secreted interleukins IL-5, IL-10 and IL-4, and is correlated with the levels of these T-h -derived molecules, while it does not involve the ligation of the BCR/CD19 complex. We suggest that the effect might reflect the situation occurring in vivo as the homeostatic proliferation of otherwise non-stimulated, peripheral B lymphocytes, providing an always ready pool for efficient antibody production to any new (or cognate) antigen challenge.