期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 91, 期 -, 页码 578-586出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2020.09.014
关键词
Stroke; IgA; Chronic inflammation; Thymus-independent type 2 antigen; Cognitive decline; B-lymphocytes; CD4+helper T-lymphocytes
资金
- NIH [R01NS096091, R01AI099108, R01AI129945, F31NS105455, T32AG058503-01A1]
- United States Department of Veterans Affairs [I01RX003224]
- Foundation Leducq Transatlantic Network of Excellence
- Phoenix Chapter of ARCS Foundation, Inc.
The text explores the activation of B-lymphocytes following stroke and their involvement in cognitive decline. The study found that B-lymphocytes, T-lymphocytes, and plasma cells progressively infiltrate the infarct between 2 and 7 weeks after stroke. Additionally, a population of IgA + plasma cells develop independently of CD4 + helper T-lymphocytes and MyD88 signaling, producing natural antibodies.
Up to 30% of stroke patients experience cognitive decline within one year of their stroke. There are currently no FDA-approved drugs that can prevent post-stroke cognitive decline, in part due to a poor understanding of the mechanisms involved. We have previously demonstrated that a B-lymphocyte response to stroke, marked by IgA + cells, can cause delayed cognitive dysfunction in mice and that a similar adaptive immune response occurs in the brains of some human stroke patients that suffer from vascular dementia. The stimuli which trigger B-lymphocyte activation following stroke, and their target antigens, are still unknown. Therefore, to learn more about the mechanisms by which B-lymphocytes become activated following stroke we first characterized the temporal kinetics of the B-lymphocyte, T-lymphocyte, and plasma cell (PC) response to stroke in the brain by immunohistochemistry (IHC). We discovered that B-lymphocyte, T-lymphocyte, and plasma cell infiltration within the infarct progressively increases between 2 and 7 weeks after stroke. We then compared the B-lymphocyte response to stroke in WT, MHCII-/-, CD4(-/-), and MyD88(-/-) mice to determine if B-lymphocytes mature into IgA + PCs through a T-lymphocyte and MyD88 dependent mechanism. Our data from a combination of IHC and flow cytometry indicate that following stroke, a population of IgA + PCs develops independently of CD4 + helper T-lymphocytes and MyD88 signaling. Subsequent sequencing of immunoglobulin genes of individual IgA + PCs present within the infarct identified a novel population of natural antibodies with few somatic mutations in complementarity-determining regions. These findings indicate that a population of IgA + PCs develops in the infarct following stroke by B-lymphocytes interacting with one or more thymus independent type 2 (TI-2) antigens, and that they produce IgA natural antibodies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据