Williams M B, Rosé J R, Rott L S, Franco M A, Greenberg H B, Butcher E C
Department of Pathology, Digestive Disease Center, Stanford University, CA 94305, USA.
J Immunol. 1998 Oct 15;161(8):4227-35.
Infection of mice with murine rotaviruses induces life-long immunity, characterized by high levels of IgA in the intestine and large numbers of rotavirus (RV)-specific Ab-secreting cells in gut-associated lymphoid tissues. Lymphocyte trafficking into gut-associated lymphoid tissues is mediated by interaction of the alpha4beta7 integrin on lymphocytes with the vascular mucosal addressin cell adhesion molecule-1. To determine whether B cell memory for RV correlates with alpha4beta7 expression, we transferred sorted B220+ phenotypically defined memory (IgD- alpha4beta7(high) and IgD- alpha4beta7-) and naive (IgD+ alpha4beta7+) splenocytes into recombination-activating gene-2 knockout mice (B and T cell-deficient) that were chronically infected with RV. Only mice receiving alpha4beta7(high) memory (IgD-) B cells produced RV-specific IgA in the stool, cleared the virus, and were immune to reinfection. Alpha4beta7(high) (but not alpha4beta7-) memory B cells from donors boosted as much as 7 mo previously also cleared the virus, indicating that alpha4beta7(high) memory B cells maintain long term functional immunity to RV. Although only alpha4beta7(high) memory cells provided mucosal immunity, alpha4beta7- cells from recently boosted donor animals could generate RV-specific serum IgG, but, like naive (IgD+) B cells, were unable to induce viral clearance even 60 days after cell transfer. These data indicate that protective immunity for an intestinal pathogen, RV, resides in memory phenotype B cells expressing the intestinal homing receptor, alpha4beta7.
用鼠轮状病毒感染小鼠可诱导终身免疫，其特征是肠道中高水平的IgA以及肠道相关淋巴组织中大量的轮状病毒（RV）特异性抗体分泌细胞。淋巴细胞向肠道相关淋巴组织的迁移是由淋巴细胞上的α4β7整合素与血管黏膜地址素细胞黏附分子-1的相互作用介导的。为了确定对RV的B细胞记忆是否与α4β7表达相关，我们将分选的表型定义为记忆（IgD-α4β7（高）和IgD-α4β7-）和幼稚（IgD+α4β7+）的脾细胞转移到慢性感染RV的重组激活基因-2敲除小鼠（B和T细胞缺陷）中。只有接受α4β7（高）记忆（IgD-）B细胞的小鼠在粪便中产生RV特异性IgA，清除病毒，并对再感染具有免疫力。来自7个月前增强免疫的供体的α4β7（高）（而非α4β7-）记忆B细胞也能清除病毒，这表明α4β7（高）记忆B细胞维持对RV的长期功能性免疫。虽然只有α4β7（高）记忆细胞提供黏膜免疫，但来自近期增强免疫的供体动物的α4β7-细胞可产生RV特异性血清IgG，但与幼稚（IgD+）B细胞一样，即使在细胞转移60天后也无法诱导病毒清除。这些数据表明，针对肠道病原体RV的保护性免疫存在于表达肠道归巢受体α4β7的记忆表型B细胞中。
