Neonatal FcR Overexpression Boosts Humoral Immune Response in Transgenic Mice
Neonatal FcR Overexpression Boosts Humoral Immune Response in Transgenic Mice
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DOI：
10.4049/jimmunol.1000353
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发表时间：
2011-01-15
影响因子：
4.4
通讯作者：
Kacskovics, Imre
中科院分区：
文献类型：
--
作者：
Cervenak, Judit;Bender, Balazs;Kacskovics, Imre
新生儿FcR（FcRn）调节IgG和白蛋白的稳态，介导母体IgG转运，积极参与吞噬作用，并递送Ag用于呈递。我们先前已经表明，转基因（Tg）小鼠中FcRn的过表达通过减少其清除延长了小鼠IgG的半衰期。在本文中，我们证明，用OVA和三硝基苯基偶联的人IgG免疫这些小鼠，会导致血清中Ag特异性IgM和IgG增加3至10倍。IgM增加是意外的，因为FcRn不结合IgM。我们的结果表明，Ag特异性IgG的亲和力在Tg小鼠中至少与野生型（wt）对照中一样好，这意味着两组中的亲和力成熟都适当。流感疫苗接种产生了2倍的Tg动物中的病毒特异性抗体的量的增加，这证明是在野生型对照的情况下，在血凝抑制试验中的效率的两倍。免疫后，Tg小鼠显示出显着更大的脾脏含有更多数量的Ag特异性B细胞和浆细胞，以及更多的粒细胞和树突状细胞，ELISPOT和流式细胞术研究分析。从这些Tg小鼠的中性粒细胞表达的Tg FcRn和吞噬IgG免疫复合物更有效地比野生型小鼠。这些结果表明，FcRn过表达不仅延长了IgG半衰期，而且增强了Ag特异性B细胞和浆细胞的扩增。虽然这两种效应都增加了Ag特异性IgG的水平，但与IgG清除率降低相比，免疫应答和IgG产生的增加似乎更为突出。免疫学杂志，2011，186：959-968。
The neonatal FcR (FcRn) regulates IgG and albumin homeostasis, mediates maternal IgG transport, takes active part in phagocytosis, and delivers Ag for presentation. We have previously shown that overexpression of FcRn in transgenic (Tg) mice extends the half-life of mouse IgG by reducing its clearance. In this paper, we demonstrate that immunization of these mice with OVA and trinitrophenyl-conjugated human IgG results in a 3- to 10-fold increase of Ag-specific IgM and IgG in serum. The IgM increase was unexpected because FcRn does not bind IgM. Our results showed that the affinity of the Ag-specific IgG was at least as good in Tg mice as in the wild-type (wt) controls, implying appropriate affinity maturation in both groups. Influenza vaccination produced a 2-fold increase in the amount of virus-specific Ab in Tg animals, which proved twice as efficient in a hemagglutination inhibition assay as was the case in wt controls. After immunization, Tg mice displayed significantly larger spleens containing a higher number of Ag-specific B cells and plasma cells, as well as many more granulocytes and dendritic cells, analyzed by ELISPOT and flow cytometric studies. The neutrophils from these Tg mice expressed the Tg FcRn and phagocytosed IgG immune complexes more efficiently than did those from wt mice. These results show that FcRn overexpression not only extends the IgG half-life but also enhances the expansion of Ag-specific B cells and plasma cells. Although both effects increase the level of Ag-specific IgG, the increase in immune response and IgG production seems to be more prominent compared with the reduced IgG clearance. The Journal of Immunology, 2011, 186: 959-968.