Infection-induced marginal zone B cell production of Borrelia hermsii-specific antibody is impaired in the absence of CD1d
Infection-induced marginal zone B cell production of Borrelia hermsii-specific antibody is impaired in the absence of CD1d
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DOI：
10.4049/jimmunol.174.9.5681
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
Bockenstedt, LK
中科院分区：
文献类型：
--
作者：
Belperron, AA;Dailey, CM;Bockenstedt, LK
在没有T细胞帮助的情况下产生的Ab是针对伯氏疏螺旋体和赫氏疏螺旋体感染的关键宿主防御。我们以前已经表明，CD 1d缺陷（CD 1d（-/-））小鼠对B感染的抵抗力受损。burgdorferi。在小鼠中，CD 1d表达在边缘区B（MZ B）细胞上最高，该细胞产生针对血液传播的Ag的Ab。在这项研究中，我们研究了MZ B细胞活化和抗体生产的小鼠感染B。hermsii，其实现高水平菌血症。我们通过流式细胞术显示MZ B细胞与B结合。hermsii和上调活化标志物多配体蛋白聚糖I和B7.1在感染的16小时内。到24 h，MZ B细胞分泌B。hermsii特异性IgM，与活化标志物表达的丧失和螺旋体负荷的减少一致。相比之下，来自CD 1d（-/-）小鼠的MZ B细胞在感染后至少96小时内保持活化，但仅产生最少的B。体内和离体的赫氏特异性IgM;血液中的病原体负荷也保持升高。使用抗LFA-1和α（4）β（1）整联蛋白的mAb耗尽MZ B细胞的野生型小鼠具有降低的B血清水平。hermsii特异性IgM和增加的病原体负荷，与B相似。hermsii感染的CD 1d（-/-）小鼠。将免疫小鼠血清（而不是幼稚小鼠血清）被动转移到感染的CD 1 d（-/-）小鼠中会导致激活标志物的下调和B的清除。hermsii从MZB细胞。这些结果表明，血液传播的螺旋体激活MZB细胞产生病原体特异性IgM，并揭示了CD 1d在这一过程中的作用。免疫学杂志，2005年。
Ab that arise in the absence of T cell help are a critical host defense against infection with the spirochetes Borrelia burgdorferi and Borrelia hermsii. We have previously shown that CD1d-deficient (CD1d(-/-)) mice have impaired resistance to infection with B. burgdorferi. In mice, CD1d expression is highest on marginal zone B (MZB) cells, which produce Ab to blood-borne Ag. In this study we examined MZB cell activation and Ab production in mice infected with B. hermsii, which achieve high levels of bacteremia. We show by flow cytometry that MZB cells associate with B. hermsii and up-regulate the activation markers syndecan I and B7.1 within 16 h of infection. By 24 h, MZB cells secrete B. hermsii-specific IgM, coinciding with the loss of activation marker expression and the reduction in spirochete burden. In contrast, MZB cells from CD1d(-/-) mice remain activated for at least 96 h of infection, but produce only minimal B. hermsii-specific IgM in vivo and ex vivo; pathogen burden in the blood also remains elevated. Wild-type mice depleted of MZB cells using mAb to LFA-1 and alpha(4)beta(1) integrin have reduced serum levels of B. hermsii-specific IgM and increased pathogen burden, similar to B. hermsii-infected CD1d(-/-) mice. Passive transfer of immune mouse serum, but not naive mouse serum, into infected CD1d(-/-) mice leads to down-regulation of activation markers and clearance of B. hermsii from the MZB cells. These results demonstrate that blood-borne spirochetes activate MZB cells to produce pathogenspecific IgM and reveal a role for CD1d in this process. The Journal of Immunology, 2005.