Conventional B2 B Cell Depletion Ameliorates whereas Its Adoptive Transfer Aggravates Atherosclerosis
Conventional B2 B Cell Depletion Ameliorates whereas Its Adoptive Transfer Aggravates Atherosclerosis
复制标题
DOI：
10.4049/jimmunol.1000033
复制
发表时间：
2010-10-01
影响因子：
4.4
通讯作者：
Toh, Ban-Hock
中科院分区：
文献类型：
--
作者：
Kyaw, Tin;Tay, Christopher;Toh, Ban-Hock
动脉粥样硬化是一种慢性炎性动脉疾病，其特征在于脂质和炎性细胞的局灶性积聚。它是西方世界死亡的头号原因，因为它的心脏病发作和中风并发症。他汀类药物仅对约三分之一的患者有效，这突出表明迫切需要额外的治疗。在人和小鼠的动脉粥样硬化病变和主动脉外膜中积累的B细胞被认为可以防止动脉粥样硬化的发展。出乎意料的是，我们发现，在载脂蛋白E缺陷（ApoE（-/-））小鼠中，使用针对小鼠CD 20的充分表征的mAb进行选择性B细胞耗竭可减少动脉粥样硬化的发生和进展，而不影响高脂饮食引起的高脂血症。将5 × 10（6）或5 × 10（7）个常规B2 B细胞（而不是5 × 10（6）个B1 B细胞）连续转移到淋巴细胞缺陷型ApoE（-/-）Rag-2（-/-）共同细胞因子受体γ链缺陷型小鼠（高脂饮食喂养）中，动脉粥样硬化增加了72%。将5 × 10（6）B2 B细胞转移至仅B细胞缺陷的ApoE（-/-）小鼠，动脉粥样硬化加重> 300%。我们的研究结果提供了令人信服的证据，迄今尚未认识到的促动脉粥样硬化的作用，传统的B2细胞。这些数据表明，B2细胞可以有效地促进动脉粥样硬化的发展完全靠自己的所有其他淋巴细胞群体的完全缺乏。此外，在T细胞和所有其他淋巴细胞群存在的情况下，这些B2细胞也可以显著增强动脉粥样硬化的发展。我们的发现提高了B细胞耗竭作为抑制人类动脉粥样硬化发展和进展的治疗方法的前景。免疫学杂志，2010，185：4410-4419。
Atherosclerosis is a chronic inflammatory arterial disease characterized by focal accumulation of lipid and inflammatory cells. It is the number one cause of deaths in the Western world because of its complications of heart attacks and strokes. Statins are effective in only approximately one third of patients, underscoring the urgent need for additional therapies. B cells that accumulate in atherosclerotic lesions and the aortic adventitia of humans and mice are considered to protect against atherosclerosis development. Unexpectedly, we found that selective B cell depletion in apolipoprotein E-deficient (ApoE(-/-)) mice using a well-characterized mAb to mouse CD20 reduced atherosclerosis development and progression without affecting the hyperlipidemia imposed by a high-fat diet. Adoptive transfer of 5 x 10(6) or 5 x 10(7) conventional B2 B cells but not 5 x 10(6) B1 B cells to a lymphocyte-deficient ApoE(-/-) Rag-2(-/-) common cytokine receptor gamma-chain-deficient mouse that was fed a high-fat diet augmented atherosclerosis by 72%. Transfer of 5 x 10(6) B2 B cells to an ApoE(-/-) mouse deficient only in B cells aggravated atherosclerosis by >300%. Our findings provide compelling evidence for the hitherto unrecognized proatherogenic role of conventional B2 cells. The data indicate that B2 cells can potently promote atherosclerosis development entirely on their own in the total absence of all other lymphocyte populations. Additionally, these B2 cells can also significantly augment atherosclerosis development in the presence of T cells and all other lymphocyte populations. Our findings raise the prospect of B cell depletion as a therapeutic approach to inhibit atherosclerosis development and progression in humans. The Journal of Immunology, 2010, 185: 4410-4419.