Complement-activating IgM enhances the humoral but not the T cell immune response in mice.

Complement-activating IgM enhances the humoral but not the T cell immune response in mice.
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DOI:
10.1371/journal.pone.0081299
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Heyman B
Heyman B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ding Z;Bergman A;Rutemark C;Ouchida R;Ohno H;Wang JY;Heyman B

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当与特定抗原一起施用时,特异于该抗原的IgM抗体可以增强抗体应答,这一过程被认为需要IgM的补体激活。然而,最近的数据显示,敲入小鼠品系Cμ13,其仅产生不能激活补体的IgM,具有正常的抗体应答。此外,最近发现的鼠IgM Fc受体(FcµR或TOSO/FAIM 3)显示出影响抗体应答。这促使人们重新研究特异性IgM的补体激活是否确实是增强抗体应答所必需的,以及Cµ13 IgM的突变是否也会导致与FcµR结合受损。结果表明,来自Cµ13和野生型小鼠的IgM与鼠FcµR的结合同样良好。尽管如此,与野生型IgM相比,特异性Cμ13 IgM与绵羊红细胞或钥孔帽贝血细胞一起给药对抗体和生发中心应答的增强作用非常差。在免疫后几秒钟内,野生型IgM诱导C3沉积在血液中的绵羊红细胞上。IgM有效地增强了T依赖性体液免疫应答,但对特异性CD 4 + T细胞的活化没有影响,如通过细胞数量、细胞分裂、母细胞转化或体内活化标志物LFA-1和CD 44的表达所测量的。这些观察结果证实了补体对特异性IgM增强抗体应答的能力的重要性,并表明IgM对T细胞和B细胞应答的调节之间存在分歧。
IgM antibodies specific for a certain antigen can enhance antibody responses when administered together with this antigen, a process believed to require complement activation by IgM. However, recent data show that a knock-in mouse strain, Cμ13, which only produces IgM unable to activate complement, has normal antibody responses. Moreover, the recently discovered murine IgM Fc receptor (FcµR or TOSO/FAIM3) was shown to affect antibody responses. This prompted the re-investigation of whether complement activation by specific IgM is indeed required for enhancement of antibody responses and whether the mutation in Cµ13 IgM also caused impaired binding to FcµR. The results show that IgM from Cµ13 and wildtype mice bound equally well to the murine FcµR. In spite of this, specific Cμ13 IgM administered together with sheep red blood cells or keyhole limpet hemocyanine was a very poor enhancer of the antibody and germinal center responses as compared with wildtype IgM. Within seconds after immunization, wildtype IgM induced deposition of C3 on sheep red blood cells in the blood. IgM which efficiently enhanced the T-dependent humoral immune response had no effect on activation of specific CD4+ T cells as measured by cell numbers, cell division, blast transformation, or expression of the activation markers LFA-1 and CD44 in vivo. These observations confirm the importance of complement for the ability of specific IgM to enhance antibody responses and suggest that there is a divergence between the regulation of T- and B-cell responses by IgM.
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