Pierce N F, Cray W C
J Immunol. 1982 Mar;128(3):1311-5.
The origin and fate of specific IgA plasma cells in intestinal lamina propria were studied in rats immunized enterically with cholera toxin (CT). Our major goal was to define how an anti-CT response is focused and sustained at the site of antigen challenge. To distinguish antigen-dependent from antigen-independent mechanisms, CT exposure was restricted to defined portions of intestine and, in some studies, the distribution of antitoxin-containing plasma cells (ACC) was examined in nonimmune adoptive recipients of post-challenge thoracic duct lymphocytes. After enteric priming and challenge, ACC appeared throughout the gut, but were most numerous at the challenged site. About 25% of ACC appearing at the site of jejunal challenge were due to antigen-driven proliferation of memory cells within the lamina propria; the remainder arose elsewhere, apparently in mucosal follicles or mesenteric lymph nodes, and migrated systemically as antitoxin-containing plasmablasts before homing to the lamina propria. The homing of these migrating ACC precursors was not affected by mucosal exposure to CT, nor did they undergo appreciable antigen-driven division after arrival in gut lamina propria. However, homing was specific for the organ from which they arose, i.e., precursors arising from duodenal challenge homed selectively to jejunum, whereas those from colonic challenge homed to the colon. The organ specificity of homing was determined during the challenge response and was independent of the origin of memory cells participating in the response. The survival of migrating ACC precursors did not differ in segments of gut exposed or nonexposed to CT. However, CT exposure at the time of their migration evoked another secondary-type response, due to stimulation of comigrating memory cells, thus sustaining the secondary response at a high level. These results and those in a previous report identify important mechanisms that affect the localization, magnitude, and duration of a specific IgA response, at least in the intestine. These include: 1) organ-specific homing of migrating IgA plasmablasts, 2) antigen-driven generation of IgA plasma cells from memory cells within the lamina propria, 3) enhanced memory at the site of mucosal priming compared to that a distant mucosae, and 4) regeneration of memory cells during the secondary response.
在经肠道用霍乱毒素（CT）免疫的大鼠中，研究了肠固有层中特异性IgA浆细胞的起源和命运。我们的主要目标是确定抗CT反应如何在抗原攻击部位聚焦并持续。为了区分抗原依赖性机制和非抗原依赖性机制，将CT暴露限制在肠道的特定部位，并且在一些研究中，在接受攻击后胸导管淋巴细胞的非免疫过继受体中检查了含抗毒素浆细胞（ACC）的分布。经肠道启动和攻击后，ACC出现在整个肠道中，但在攻击部位数量最多。出现在空肠攻击部位的ACC中约25%是由于固有层内记忆细胞的抗原驱动增殖；其余的则在其他地方产生，显然是在黏膜滤泡或肠系膜淋巴结中，并在归巢到固有层之前作为含抗毒素的成浆细胞进行全身迁移。这些迁移的ACC前体细胞的归巢不受黏膜暴露于CT的影响，它们在到达肠固有层后也没有经历明显的抗原驱动分裂。然而，归巢对它们产生的器官具有特异性，即来自十二指肠攻击的前体细胞选择性地归巢到空肠，而来自结肠攻击的前体细胞归巢到结肠。归巢的器官特异性在攻击反应期间确定，并且与参与反应的记忆细胞的起源无关。迁移的ACC前体细胞在暴露或未暴露于CT的肠道段中的存活没有差异。然而，它们迁移时暴露于CT会引发另一种二次型反应，这是由于共迁移的记忆细胞受到刺激，从而使二次反应维持在高水平。这些结果以及先前报告中的结果确定了至少在肠道中影响特异性IgA反应的定位、强度和持续时间的重要机制。这些机制包括：1）迁移的IgA成浆细胞向器官的特异性归巢；2）固有层内记忆细胞通过抗原驱动产生IgA浆细胞；3）与远处黏膜相比，黏膜启动部位的记忆增强；4）二次反应期间记忆细胞的再生。
