Protective intestinal anti-rotavirus B cell immunity is dependent on α4β7 integrin expression but does not require IgA antibody production
Protective intestinal anti-rotavirus B cell immunity is dependent on α4β7 integrin expression but does not require IgA antibody production
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DOI：
10.4049/jimmunol.166.3.1894
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发表时间：
2001-02-01
影响因子：
4.4
通讯作者：
Greenberg, HB
中科院分区：
文献类型：
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作者：
Kuklin, NA;Rott, L;Greenberg, HB
轮状病毒（RV）是幼儿严重胃肠炎的主要原因;保护与肠道Ab反应相关。使用RV感染的小鼠模型和不表达α 4 β 7整联蛋白的β 7缺陷（β 7-/-）小鼠，我们证明了α 4 β 7整联蛋白在B细胞介导的抗RV免疫中的重要性。急性感染鼠RV的β（-/-）（7）小鼠的感染消退，并产生正常的血清IgG抗体，但肠道伊加反应减弱。α（4）β（-/-）（7）免疫B细胞在过继转移到RV感染的Rag-2缺陷小鼠中时不能解决RV感染。与野生型相比，在用β（-/-）（7）B细胞转移的Rag-2缺陷小鼠的肠道中发现更少的RV特异性B细胞。在转移的β（-/-）（7）B细胞中，α（4）β（7）表达的缺乏和/或IgA产生细胞的频率较低可能是这些细胞在被动转移后不能解决RV感染的原因。为了区分这些可能性，我们使用IgA缺陷（伊加（-/-））小鼠研究了伊加产生在RV感染中的重要性。CD 8（+）T细胞耗竭的伊加-/-小鼠能够清除原发性RV感染。同样，过继转移免疫伊加（-/-）B细胞到慢性感染的Rag-2缺陷小鼠解决RV感染。我们在野生型和伊加（-/-）小鼠中进一步证明，口服RV感染后，保护性B细胞存在于α（4）β（高）（7）群体中。我们的研究结果表明，α（4）β（7）整合素的表达是B细胞介导的RV免疫所必需的，而不依赖于伊加的存在。
Rotavirus (RV) is the main cause of severe gastroenteritis in young children; protection has been correlated with intestinal Ab responses. Using a mouse model of RV infection and beta (7)-deficient (beta (-/-)(7)) mice, which do not express alpha (4)beta (7) integrin, we demonstrated the importance of alpha (4)beta (7) integrin in B cell-mediated anti-RV immunity. beta (-/-)(7) mice acutely infected with murine RV resolved infection and developed normal serum IgG Abs but had diminished intestinal IgA responses. alpha (4)beta (-/-)(7) immune B cells did not resolve RV infection when adoptively transferred into RV-infected Rag-2-deficient mice. Fewer RV-specific B cells were found in the intestine of Rag-2-deficient mice transferred with beta (-/-)(7) B cells compared with wild type. The absence of alpha (4)beta (7) expression and/or a lower frequency of IgA-producing cells among transferred beta (-/-)(7) B cells could have accounted for the inability of these cells to resolve RV infection following passive transfer, To distinguish between these possibilities, we studied the importance of IgA production in RV infection using IgA-deficient (IgA(-/-)) mice. IgA-/- mice depleted of CD8(+) T cells were able to clear primary RV infection. Similarly, adoptive transfer of immune IgA(-/-) B cells into chronically infected Rag-2-deficient mice resolved RV infection. We further demonstrated in both wild-type and IgA(-/-) mice that, following oral RV infection, protective B cells reside in the alpha (4)beta (high)(7) population. Our findings suggest that alpha (4)beta (7) integrin expression is necessary for B cell-mediated immunity to RV independent of the presence of IgA.