B cell depletion curtails CD4+ T cell memory and reduces protection against disseminating virus infection.

B cell depletion curtails CD4+ T cell memory and reduces protection against disseminating virus infection.
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DOI:
10.4049/jimmunol.1302661
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发表时间:
2014-02-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Whitmire JK
Whitmire JK
中科院分区:
其他
文献类型:
--
作者:
Misumi I;Whitmire JK

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CD4+ T 细胞和 B 细胞之间的动态相互作用是体液免疫和 CD4+ T 细胞记忆所必需的。目前尚不清楚早期需要 B 细胞来诱导记忆前体细胞的形成,还是稍后需要 B 细胞来维持记忆细胞。在此,在急性淋巴细胞性脉络膜脑膜炎病毒(LCMV)感染之前或之后不同时间,通过抗CD20耗尽成熟B细胞的野生型小鼠中,追踪原代和记忆CD4+T细胞反应。抗体治疗导致 B 细胞数量减少 1000 倍,持续 6 周。在 B 细胞耗尽的小鼠中产生原代病毒特异性 CD4+ Th1 细胞,然而,CD4+Ly6CloTbet+ 记忆前体细胞群减少,CD4+ 记忆细胞数量相应减少 4 倍。记忆 T 细胞在没有 B 细胞的情况下形成时,细胞因子的产生受到损害。 B 细胞耗竭对已建立的记忆群体没有影响。在病毒感染传播过程中,B 细胞耗竭导致持续体重减轻、CD4+ 和 CD8+ T 细胞功能衰竭,并阻止小鼠消除感染。因此,B 细胞有助于急性感染后记忆 CD4+ T 细胞的建立和存活,并在针对传播性病毒感染的免疫保护中发挥重要作用。
Dynamic interactions between CD4+ T cells and B cells are needed for humoral immunity and CD4+ T cell memory. It is not known whether B cells are needed early on to induce the formation of memory precursor cells or are needed later to sustain memory cells. Herein, primary and memory CD4+ T cells responses were followed in wildtype mice that were depleted of mature B cells by anti-CD20 before or different times after acute lymphocytic choriomeningitis virus (LCMV) infection. The antibody treatment led to a 1000-fold reduction in B cell number that lasted 6 weeks. Primary virus-specific CD4+ Th1 cells were generated in B cell-depleted mice, however, there was a decrease in the CD4+Ly6CloTbet+ memory precursor population and a corresponding 4-fold reduction in CD4+ memory cell number. Memory T cells showed impaired cytokine production when they formed without B cells. B cell-depletion had no effect on established memory populations. During disseminating virus infection, B cell depletion led to sustained weight loss, functional exhaustion of CD4+ and CD8+ T cells, and prevented mice from resolving the infection. Thus, B cells contribute to the establishment and survival of memory CD4+ T cells following acute infection and play an essential role in immune protection against disseminating virus infection.
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