IgA natural antibodies are produced following T-cell independent B-cell activation following stroke
| Autor: | Deepta Bhattacharya, Jessica Stokes, Jacob C. Zbesko, Danielle A. Becktel, Jennifer B. Frye, Kylie Calderon, Diana K. Gerardo, Kristian P. Doyle, Thuy-Vi V. Nguyen |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes T cell Immunology Population Cognitive decline Plasma cell Lymphocyte Activation Article Thymus-independent type 2 antigen 03 medical and health sciences Behavioral Neuroscience Mice 0302 clinical medicine Antigen Medicine Animals Humans cardiovascular diseases education Vascular dementia Stroke education.field_of_study B-Lymphocytes Endocrine and Autonomic Systems business.industry Chronic inflammation Acquired immune system medicine.disease Immunoglobulin A 030104 developmental biology medicine.anatomical_structure business 030217 neurology & neurosurgery IgA CD4+ helper T-lymphocytes |
| Zdroj: | Brain, behavior, and immunity |
| ISSN: | 1090-2139 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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