Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse
Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse
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DOI：
10.1182/blood-2006-10-053793
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发表时间：
2007-09-01
期刊：
影响因子：
20.3
通讯作者：
Gunzer, Matthias
中科院分区：
文献类型：
--
作者：
Reichardt, Peter;Dornbach, Bastian;Gunzer, Matthias
幼稚B细胞是无效的抗原呈递细胞，被认为不能激活幼稚T细胞。然而，这些细胞的抗原特异性接触导致稳定的细胞对在体内保持联系数小时。这类配对的生理作用尚未得到评估。我们在这里表明，在初始B细胞和初始T细胞之间的抗原特异性偶联物在接触区显示出成熟的免疫突触，这在T细胞-树突状细胞（DC）对中是不存在的。B细胞诱导大量增殖，但与dc相反，T细胞中没有l -选择素的损失。令人惊讶的是，当dc触发的T细胞发育为正常效应细胞时，b细胞刺激超过72小时诱导调节性T细胞以接触依赖的方式抑制新鲜T细胞的启动。在体内，调节性T细胞回到淋巴结，在那里它们有效地抑制免疫反应，如皮肤过敏和异位异体心脏移植排斥反应。我们的发现可能有助于解释B细胞诱导耐受性的旧观察，确定成熟的免疫突触是这一过程的核心功能模块，并建议使用幼稚B细胞启动的调节性T细胞（“bTregs”）作为治疗干预不良适应性免疫反应的有用方法。
Naive B cells are ineffective antigen presenting cells and are considered unable to activate naive T cells. However, antigen-specific contact of these cells leads to stable cell pairs that remain associated over hours in vivo. The physiologic role of such pairs has not been evaluated. We show here that antigen-specific conjugates between naive B cells and naive T cells display a mature immunologic synapse in the contact zone that is absent in T-cell-dendritic cell (DC) pairs. B cells induce substantial proliferation but, contrary to DCs, no loss of L-selectin in T cells. Surprisingly, while DC-triggered T cells develop into normal effector cells, B-cell stimulation over 72 hours induces regulatory T cells inhibiting priming of fresh T cells in a contact-dependent manner in vitro. In vivo, the regulatory T cells home to lymph nodes where they potently suppress immune responses such as in cutaneous hypersensitivity and ectopic allogeneic heart transplant rejection. Our finding might help to explain old observations on tolerance induction by B cells, identify the mature immunologic synapse as a central functional module of this process, and suggest the use of naive B-cell-primed regulatory T cells, "bTregs," as a useful approach for therapeutic intervention in adverse adaptive immune responses.