Study of the mucosal immunomoduLation by intestinal commensal bacteria

肠道共生菌在调节肠道抗过敏反应、抗感染等免疫应答中起着重要作用。研究表明，肠道共生菌极大地影响肠道相关淋巴组织的发育和粘膜免疫反应，如肠道中IgA的产生。鉴于大量的肠道微生物群，特别是在大肠中，人们认为大肠中的免疫细胞是由微生物调节的。虽然免疫细胞在小肠中产生IgA已经被研究过，但是在大肠中产生IgA却知之甚少。在这项研究中，我们发现存在于大肠中的微生物诱导淋巴细胞产生IgA。从无菌（GF）和常规（CV）小鼠中分离大肠固有层淋巴细胞（L-LP）。采用流式细胞术分析L-LP淋巴细胞中IgM+B220+细胞、IgA+B220+细胞和IgA+ syndecan - 1 +B220-细胞的频率。此外，为了确定共生菌的刺激是否影响IgM+细胞向iga -浆细胞的分化，我们将GF小鼠L-LP淋巴细胞分离的IgM+细胞与CV小鼠肠道共生菌分离的嗜酸拟杆菌（Bacteroides acid faciens）共培养。GF小鼠L-LP中IgA+Syndecan-1+B220-细胞和IgA+B220 -细胞的频率均低于CV小鼠，而GF小鼠L-LP中IgM+13220+细胞的频率与CV小鼠无显著差异。受嗜酸芽胞杆菌刺激的IgM+细胞的IgA产量高于未受细菌刺激的细胞。这些结果表明，大肠杆菌的直接刺激可诱导IgM+细胞向产生iga的浆细胞分化。这也提示大肠中IgA的产生可能是由肠道共生菌诱导的，肠道微生物促进了大肠中IgM向IgA的转换。少

Intestinal commensal bacteria play important roles in the regulation of intestinal immune responses such as anti-allergic reaction and anti-infection. It has been shown that intestinal commensal bacteria greatly affect the development of gut-associated lymphoid tissues and mucosal immune responses, such as IgA production, in the gut. Given the large numbers of intestinal microbiota, particularly in the large intestine, it is believed that immunocytes in the large intestine are modulated by microbacteria. While IgA production by immunocytes in the small intestine has been previously studied, IgA production in the large intestine is, however, poorly understood. In this study, we show that IgA production by lymphocytes is induced by microbacteria present in the large intestine.Lamina propria lymphocytes from the large intestine (L-LP) were isolated from germ-free (GF) and conventional (CV) mice. Flow cytometric analysis of L-LP lymphocytes was used to assess the frequency of IgM+B220+ cel … More ls, IgA+B220+ cells, and IgA+Syndecan-l+B220- cells. In addition, to determine whether stimulation by commensal bacteria influences differentiation of IgM+ cells into IgA-plasma cells, IgM+ cells separated from L-LP lymphocytes of GF mice were co-cultured with Bacteroides acidofaciens isolated from intestinal commensal bacteria of CV mice.The frequency of IgA+Syndecan-1+B220- cells and IgA+B220+ cells in L-LP of GF were all lower than that of CV mice, but there was no difference in the frequency of IgM+13220+ cells in L-LP between GF and CV mice. IgA production by IgM+ cells stimulated by B. acidofaciens was higher than in those without bacterial stimulation.These results indicate that direct stimulation by B. acidofaciens induces differentiation of IgM+ cells into IgA-producing plasma cells from the large intestine. These also suggest that IgA production in the large intestine might be induced by intestinal commensal bacteria, thus intestinal microbacteria promote the class switching from IgM to IgA in the large intestine. Less