Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers.
Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers.
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DOI：
10.4049/jimmunol.1502034
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发表时间：
2016-04-15
期刊：
影响因子：
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通讯作者：
Biragyn A
中科院分区：
文献类型：
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作者：
Lee-Chang C;Bodogai M;Moritoh K;Chen X;Wersto R;Sen R;Young HA;Croft M;Ferrucci L;Biragyn A
衰老中的B细胞失调被认为主要发生在传统的B2细胞中，而不影响先天的B1细胞。老年人和小鼠也积累来源不明的4-1BBL+ MHC IHi类CD 86 Hi B细胞。在这里，我们报告，这些细胞，称为4 BL细胞，是激活的小鼠和可能的人B1 a细胞。活化由老化的人单核细胞和鼠腹腔巨噬细胞介导。4 BL细胞诱导B1 a细胞上4-1BBL和IFNγR1的表达，导致随后膜TNFα（mTNFα）和CD 86的上调。因此，B1 a细胞通过mTNFα靶向TNFR 2，同时提供与CD 86的共刺激，诱导CD 8 +T细胞中颗粒酶B的表达。因此，这些结果首次表明，衰老影响B1 a细胞的功能。随着年龄的增长，这些细胞失去了它们的肿瘤支持活性，并成为潜在的抗肿瘤和自身免疫CD 8 +T细胞的诱导剂。
B-cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL+ MHC class-IHi CD86Hi B cells of unknown origin. Here we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. The 4BL cells induce expression of 4-1BBL and IFNγR1 on B1a cells resulting in subsequent up regulation of membrane TNFα (mTNFα) and CD86. As a result, B1a cells induce expression of granzyme B in CD8+T cells by targeting TNFR2 via mTNFα while providing co-stimulation with CD86. Thus, for the first time, these results indicate that aging affects the function of B1a cells. Upon aging, these cells lose their tumor-supporting activity and become inducers of potentially antitumor and autoimmune CD8+T cells.