Marginal zone B-Cell depletion impairs murine host defense against Borrelia burgdorferi infection
Marginal zone B-Cell depletion impairs murine host defense against Borrelia burgdorferi infection
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DOI：
10.1128/iai.00422-07
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发表时间：
2007-07-01
影响因子：
3.1
通讯作者：
Bockenstedt, Linda K.
中科院分区：
文献类型：
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作者：
Belperron, Alexia A.;Dailey, Catherine M.;Bockenstedt, Linda K.
边缘区B （MZB）细胞是一种B细胞亚群，可产生针对血源性抗原的不依赖t细胞的抗体。在这项研究中，我们检测了MZB细胞耗损对莱姆病螺旋体伯氏疏螺旋体免疫反应的影响，伯氏疏螺旋体是一种细胞外病原体，t细胞非依赖性抗体是宿主的重要防御。使用LFA-1和α (4) β(1)整合素单克隆抗体去除C3H/HeJ小鼠的MZB细胞，降低了伯氏疏螺旋体特异性免疫球蛋白M （IgM）滴度，增加了病原体负担，并在感染的前2周内导致更严重的关节炎。此外，MZB细胞缺失小鼠的伯氏疏螺旋体特异性IgG水平降低，这与脾脏CD4(+) t细胞活化、增殖和细胞因子产生减少有关。将感染对照小鼠的免疫小鼠血清被动转移到感染MZB细胞缺失的小鼠体内，可减少病原体负担，但不会改变脾CD4(+) T细胞上T细胞活化标记物的表达。这些发现表明MZB细胞不仅是病原体特异性IgM的来源，对限制螺旋体负担和病理很重要，而且在脾t细胞对血源性病原体的反应中起着重要作用。
Marginal zone B (MZB) cells are a B-cell subset that produces T-cell-independent antibodies to blood-borne antigens. In this study, we examined the effects of MZB cell depletion on the immune response to the Lyme disease spirochete Borrelia burgdorferi, an extracellular pathogen for which T-cell-independent antibody is an important host defense. MZB cell depletion of C3H/HeJ mice using monoclonal antibody to LFA-1 and alpha(4)beta(1) integrins reduced B. burgdorferi-specific immunoglobullin M (IgM) titers, enhanced pathogen burden, and led to more severe arthritis assessed within the first 2 weeks of infection. In addition, MZB cell-depleted mice had reduced levels of B. burgdorferi-specific IgG, which correlated with diminished splenic CD4(+) T-cell-activation, proliferation, and cytokine production. Passive transfer of immune mouse serum from infected control mice into infected MZB cell-depleted mice reduced pathogen burden but did not alter the expression of T-cell activation markers on splenic CD4(+) T cells. These findings demonstrate that MZB cells not only are a source of pathogen-specific IgM important for limiting spirochete burden and pathology but also play a prominent role in the priming of splenic T-cell responses to a blood-borne pathogen.