IgM- and IgA-response of peritoneal B-1 cells to the TI-2 antigen with the presence of γδT cells in vitro

N. Snegireva, E. Sidorova, I. Dyakov, M. Gavrilova, I. Chernyshova, E. Pashkov, O. A. Svitich
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Abstract

IgA is an important component of the mucosal system of the body. It limits penetration of pathogens into the bloodstream. Inflammatory diseases such as Crohn disease and colitis may be associated with disorders of IgA synthesis. Both B1 and B2 cells are a source of IgA in the intestines. Special attention is paid to B1 cells, which are able to respond to T-independent type 2 antigens and produce natural antibodies. B1 cells produce about 50% of the intestinal IgA including specific antibodies to the components of microorganisms contained in the gastrointestinal tract. The mechanism of IgA formation in the T-independent way is not investigated in details. It was suggested that the γδТ-cells promote switching to IgA synthesis by B1 cells. This assumption may be supported by their co-localization with B1 lymphocytes in the intestinal mucosa, as well as participation, along with B1 cells, in formation of the first-line defense against the pathogens. In addition, the both lymphocyte subpopulations evolve during initial ontogenesis, earlier than “classic” В2 and αβT cells. Therefore, it was suggested that γδT lymphocytes may be involved into the processes of induction and/or regulation of IgM and IgA production by B1 cells in response to TH2 antigens.In the present study, we have shown the effect of γδT cells upon generation of IgM- and IgA-forming B1 cells in response to α-1,3-dextran in vitro. We also studied the dynamics of the mRNA expression for IgM- and IgA-heavy chains by the B1 cells at different terms of in vitro culture.It was found that, during co-cultivation of B1 cells with 20% γδT lymphocytes, there is no increase in the number of dextran-specific IgM-producing cells. The B1 cells exhibited an increase of IgM heavy chain mRNA expression in response to dextran but not in co-cultures. Expression of mRNA for IgM heavy chains in co-cultures was decreased compared to non-treated B-cell cultures. Contrary to the earlier assumption, a presence of γδT lymphocytes in culture did not enhance the formation of IgA producents. The obtained data suggest regulatory properties of the γδТ lymphocytes during the B1 cells response to T-independent antigens. 
体外γδT细胞存在下腹膜B-1细胞对TI-2抗原的IgM和iga反应
IgA是机体粘膜系统的重要组成部分。它限制了病原体进入血液。炎性疾病如克罗恩病和结肠炎可能与IgA合成紊乱有关。B1和B2细胞都是肠道中IgA的来源。特别注意的是B1细胞,它能够对t不依赖的2型抗原作出反应并产生天然抗体。B1细胞产生约50%的肠道IgA,包括针对胃肠道中微生物成分的特异性抗体。IgA不依赖于t的形成机制没有详细研究。这表明γδТ-cells促进B1细胞向IgA合成的转换。这一假设可能是由它们与肠粘膜中的B1淋巴细胞共定位以及与B1细胞一起参与形成对抗病原体的第一线防御所支持的。此外,这两个淋巴细胞亚群在初始个体发生时进化,比“经典”В2和αβT细胞早。因此,我们认为γδT淋巴细胞可能参与了B1细胞对TH2抗原的诱导和/或调节IgM和IgA产生的过程。在本研究中,我们在体外研究了α-1,3-葡聚糖对γδT细胞生成IgM和iga形成B1细胞的影响。我们还研究了不同体外培养条件下B1细胞IgM-和iga -重链mRNA的表达动态。结果发现,在B1细胞与20% γδT淋巴细胞共培养时,右旋糖酐特异性igm产生细胞的数量没有增加。右旋糖酐使B1细胞IgM重链mRNA表达增加,而在共培养中没有。与未处理的b细胞培养相比,共培养中IgM重链mRNA的表达减少。与先前的假设相反,培养中γδT淋巴细胞的存在并没有促进IgA产物的形成。获得的数据表明γδТ淋巴细胞在B1细胞对t非依赖性抗原的反应中具有调节特性。
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