Origin and homing of intestinal IgA antibody-secreting cells.
Origin and homing of intestinal IgA antibody-secreting cells.
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DOI：
10.1084/jem.20011910
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发表时间：
2002-01-21
期刊：
影响因子：
--
通讯作者：
Phillips-Quagliata JM
中科院分区：
文献类型：
--
作者：
Lamm ME;Phillips-Quagliata JM
在生物合成的基础上，IgA构成了人体抗体的主要同型，这一事实并没有得到广泛的认识，因为IgG而不是IgA是血清中的主要同型。尽管如此，人体的大部分产生igg的细胞分布在各种粘膜和外分泌部位，特别是沿着肠道，它们中的大多数产生针对环境抗原的IgA抗体，包括当地的微生物菌群。这些抗体可以以多种方式发挥作用，作为与外部环境边界的第一道免疫防线(1)。人们早就认识到，肠道中IgA浆细胞前体的主要来源是Peyer斑块的有组织淋巴组织(2)。这里，生发中心的B细胞被认为在T细胞和细胞因子，特别是TGF-的影响下，从IgM转换为IgA（3,4）。然后它们从佩耶氏斑转移到引流的肠系膜淋巴结，在那里它们继续分裂和分化。最后它们离开淋巴结，通过胸导管进入血液，血液将它们带到肠道固有层。在这里，它们完成了向成熟的分泌iga的浆细胞的分化，这是这个位置的特征（5,6）。在这一过程中，Th2细胞因子如IL-5、IL-6和IL-10被认为在诱导转换后的B细胞产生IgA分泌中起重要作用（3,4）。关于IgA细胞周期，有两点值得强调。首先，浆细胞的前体在到达肠固有层之前就开始致力于产生IgA；其次，尽管固有层中存在抗原可以增强新到达的B细胞的增殖，但向固有层的转运不依赖于特定抗原。从机制的角度来看，是什么导致了循环中的IgA B细胞对肠道粘膜的吸引？一般认为，淋巴细胞运输的区域特异性是由一系列相互作用的局部血管内皮受体及其各自对循环淋巴细胞的反受体的净效应控制的(7)。这些相互作用被认为解释了一系列的步骤，从淋巴细胞与内皮细胞的短暂结合开始，到它们通过血管壁渗出结束。为了运输到肠道，局部小静脉上的MAdCAM-1寻址蛋白和淋巴细胞上的47整合素被认为是关键的受体-反受体对。除了淋巴细胞和血管内皮细胞之间的相互作用外，几年前有人提出，来自粘膜和/或外分泌上皮的一种因子可能选择性地吸引粘膜IgA浆细胞的循环前体，并且有证据表明存在这种对致力于IgA的B细胞具有特异性的趋化因子(8)。然而，与已发表的关于淋巴细胞和内皮受体及其相互作用的丰富分子信息形成鲜明对比的是，在确定iga承诺的B细胞或其在归巢淋巴细胞上的受体的趋化因子方面基本上没有进展。这种情况刚刚改变。在本期中，Bowman等人(9)为这种IgA B细胞趋化因子，即趋化因子胸腺表达趋化因子（TECK）（CCL25）提供了令人信服的证据。这项研究报告建立在去年发表的一项研究的基础上，在这项研究中，TECK被证明主要在小肠上皮的外周组织中产生（10）。Bowman等人(9)进一步令人信服地证明，TECK可以从脾脏、Peyer’s patches和肠系膜淋巴中吸引IgA-committed B细胞。
The fact that IgA comprises the body’s major isotype of antibody on a biosynthetic basis is not widely appreciated because IgG, not IgA, is the predominant isotype in serum. Nevertheless, the bulk of the body’s Ig-producing cells reside in the various mucosal and exocrine sites, especially along the intestinal tract, and most of them make IgA antibodies against environmental antigens, including the local microbial flora. These antibodies can then function in multiple ways as a first line of immune defense at boundaries with the external environment (1). It has long been recognized that a major source of the precursors of the IgA plasma cells in the intestine is the organized lymphoid tissue of the Peyer’s patches (2). Here B cells in the germinal centers are thought to switch from IgM to IgA under the influence of T cells and cytokines, in particular TGF-(3, 4). They then migrate from the Peyer’s patches to the draining mesenteric lymph nodes, where they continue to divide and differentiate. Finally they exit the lymph nodes and pass via the thoracic duct lymph into the blood, which carries them to the lamina propria of the gut. Here they complete their differentiation into the mature IgA-secreting plasma cells so characteristic of this location (5, 6). During this process such Th2 cytokines as IL-5, IL-6, and IL-10 are thought to be important in inducing the switched B cells to make IgA for secretion (3, 4). With regard to this IgA cell cycle, two points are worth emphasizing. One, the precursors of the plasma cells become committed to producing IgA well before they reach the intestinal lamina propria, and two, trafficking to lamina propria is independent of specific antigen even though the presence of antigen in the lamina propria can enhance the proliferation of the newly arrived B cells. From a mechanistic viewpoint, what accounts for the attraction of circulating IgA B cells to the mucosa of the gut? The paradigm has been that the regional specificity of lymphocyte trafficking is governed by the net effect of sets of interacting local vascular endothelial receptors and their respective counterreceptors on circulating lymphocytes (7).These interactions are thought to account for the series of steps that begins with transient binding of the lymphocytes to endothelium and ends with their diapedesis across the vascular wall. For trafficking to the gut, the MAdCAM-1 addressin on local venules and the 4 7 integrin on the lymphocyte are thought to be the key receptor–counterreceptor pair. In addition to interactions between moieties on lymphocytes and vascular endothelial cells, it was proposed some years ago that a factor derived from mucosal and/or exocrine epithelium might selectively attract the circulating precursors of mucosal IgA plasma cells, and evidence for the existence of such a chemotactic factor with specificity for B cells committed to IgA was presented (8). In marked contrast, however, to the wealth of molecular information that has been published on lymphocyte and endothelial receptors and their interactions, essentially no progress was forthcoming in identifying a chemotactic factor for IgA-committed B cells or its receptor on homing lymphocytes. This situation has just changed. In this issue, Bowman et al.(9) provide compelling evidence for such an IgA B cell chemotactic factor, namely the chemokine thymus-expressed chemokine (TECK)(CCL25). The research reported builds on work published last year in which TECK was shown to be produced in peripheral tissues mainly in the epithelium of the small intestine (10). Bowman et al.(9) have gone on to demonstrate convincingly that TECK can attract IgA-committed B cells from spleen, Peyer’s patches, and mesenteric lymph …
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人类胎儿大脑：B细胞产生的位置。
DOI：
10.1084/jem.175.2.397
发表时间：
1992-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Solvason N;Kearney JF
通讯作者：
Kearney JF
DOI：
10.1084/jem.20010670
发表时间：
2002-01-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bowman EP;Kuklin NA;Youngman KR;Lazarus NH;Kunkel EJ;Pan J;Greenberg HB;Butcher EC
通讯作者：
Butcher EC
影响因子：
15.3
作者：
Bowman, E P;Campbell, J J;Soler, D;Dong, Z;Manlongat, N;Picarella, D;Hardy, R R;Butcher, E C
通讯作者：
Butcher, E C
影响因子：
15.3
作者：
Kunkel, E J;Campbell, J J;Haraldsen, G;Pan, J;Boisvert, J;Roberts, A I;Ebert, E C;Vierra, M A;Goodman, S B;Genovese, M C;Wardlaw, A J;Greenberg, H B;Parker, C M;Butcher, E C;Andrew, D P;Agace, W W
通讯作者：
Agace, W W
影响因子：
15.3
作者：
CRAIG, SW;CEBRA, JJ
通讯作者：
CEBRA, JJ