Human IgA-inducing protein from dendritic cells induces IgA production by naive IgD+ B cells.

Human IgA-inducing protein from dendritic cells induces IgA production by naive IgD+ B cells.
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DOI:
10.4049/jimmunol.0801973
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发表时间:
2009-02-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Estes DM
Estes DM
中科院分区:
其他
文献类型:
--
作者:
Endsley MA;Njongmeta LM;Shell E;Ryan MW;Indrikovs AJ;Ulualp S;Goldblum RM;Mwangi W;Estes DM

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在过去的几年里,关于树突状细胞(DC)在B细胞激活和调节中的作用的研究已经取得了很大的进展。树突状细胞分泌的趋化因子可诱导B细胞向淋巴结转移。DC产生的生存因子,如BAFF和APRIL,已被证明是B细胞成熟所必需的,但也与类别转换重组和B细胞淋巴瘤的生存有关。最近添加到这个影响B细胞的DC衍生因子名单中的是IgA诱导蛋白(IGIP)。在此,我们鉴定了人DC产生IGIP的特性,并检测了其在体外诱导幼稚B细胞IgA类转换和分化的能力。体外培养单核细胞来源的DC,加入TLR激动剂(3,4,5,9)和其他因子,包括CD40L,GM-CSF,IL-4和神经肽血管活性肠肽(VIP)。在VIP和CD40L的体外刺激下,IGIP mRNA的表达在12-48小时内可上调35倍。与外源重组人免疫球蛋白一起培养的幼稚B细胞比未刺激的对照组产生更多的IgA。最后,我们证明了免疫球蛋白刺激驱动免疫球蛋白M+/免疫球蛋白+幼稚的人B细胞产生μ-α开关环,表明其作为免疫球蛋白开关因子的作用。
Over the last several years there has been a great deal of progress in characterizing the role of dendritic cells (DCs) in the activation and modulation of B cells. DC-secreted chemokines can induce B cell trafficking to the lymph nodes. DC-produced survival factors such as BAFF and APRIL have been shown to be essential for B cell maturation, but have also been implicated in class-switch recombination and B cell lymphoma survival. Recently added to this list of DC-derived factors effecting B cells is IgA-inducing protein (IGIP). Here we characterize production of IGIP by human DCs, and examine its capacity to induce IgA class switching and differentiation of naïve B cells in vitro. Monocyte derived DCS were cultured in vitro with TLR agonists (3,4,5, and 9) and other factors, including CD40L, GM-CSF, and IL-4 as well as the neuropeptide vasoactive intestinal peptide (VIP). Under in vitro stimulation with VIP and CD40L, IGIP mRNA expression could be up-regulated as much as thirty five-fold above non-stimulated samples within 12–48 hours. Naïve B cells cultured with exogenous rhIGIP produced IgA in greater quantities than non-stimulated controls. Finally, we demonstrate that IGIP stimulation drives the production of μ-α switch circles from IgM+/IgD+ naïve human B cells, indicating its role as an IgA switch factor.
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