Please use this identifier to cite or link to this item:
http://dx.doi.org/10.25673/115101
Title: | Autoantigen-selected B cells are bystanders in spontaneous T cell-driven experimental autoimmune hepatitis |
Author(s): | Lübbering, David Preti, Max Schlott, Lena Schultheiß, Christoph Weidemann, Sören Lohse, Ansgar W. Binder, Mascha Carambia, Antonella Herkel, Johannes |
Issue Date: | 2023 |
Type: | Article |
Language: | English |
Abstract: | Autoreactive B cells are considered pathogenic drivers in many autoimmune dis-eases; however, it is not clear whether autoimmune B cells are invariably patho-genic or whether they can also arise as bystanders of T cell-driven autoimmunepathology. Here, we studied the B cell response in an autoantigen- and CD4+Tcell-driven model of autoimmune hepatitis (AIH), the Alb-iGP_Smarta mouse inwhich expression of a viral model antigen (GP) in hepatocytes and its recognitionby GP-specific CD4+T cells causes spontaneous AIH-like disease. T cell-drivenAIH in Alb-iGP_Smarta mice was marked by autoantibodies and hepatic infiltra-tion of plasma cells and B cells, particularly of isotype-switched memory B cells,indicating antigen-driven selection and activation. Immunosequencing of B cellreceptor repertoires confirmed B cell expansion selectively in the liver, which wasmost likely driven by the hepatic GP model antigen, as indicated by branched net-works of connected sequences and elevated levels of IgG antibodies toGP. However, intrahepatic B cells did not produce increased levels of cytokinesand their depletion with anti-CD20 antibody did not alter the CD4+T cellresponse in Alb-iGP_Smarta mice. Moreover, B cell depletion did not preventspontaneous liver inflammation and AIH-like disease in Alb-iGP_Smarta mice. Inconclusion, selection and isotype-switch of liver-infiltrating B cells was dependenton the presence of CD4+T cells recognizing liver antigen. However, recognitionof hepatic antigen by CD4+T cells and CD4+T cell-mediated hepatitis was notdependent on B cells. Thus, autoreactive B cells can be bystanders and need notbe drivers of liver inflammation in AIH. |
URI: | https://opendata.uni-halle.de//handle/1981185920/117057 http://dx.doi.org/10.25673/115101 |
Open Access: | Open access publication |
License: | (CC BY-NC-ND 4.0) Creative Commons Attribution NonCommercial NoDerivatives 4.0 |
Journal Title: | Immunology |
Publisher: | Wiley-Blackwell |
Publisher Place: | Oxford [u.a.] |
Volume: | 170 |
Issue: | 2 |
Original Publication: | 10.1111/imm.13665 |
Page Start: | 214 |
Page End: | 229 |
Appears in Collections: | Open Access Publikationen der MLU |
Files in This Item:
File | Description | Size | Format | |
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Immunology - 2023 - Lübbering - Autoantigen‐selected B cells are bystanders in spontaneous T cell‐driven experimental.pdf | 8.43 MB | Adobe PDF | View/Open |