Immunology of persistent viral infection

Dimitrova, Mirela. Immunology of persistent viral infection. 2023, Doctoral Thesis, University of Basel, Faculty of Science.

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Perturbed B cell responses and late formation of neutralizing antibodies are hallmarks of chronic infections but the mechanisms underlying the dysfunctional humoral responses remain poorly defined. We used adoptive transfer of monoclonal anti-viral B cells (KL25) in the context of chronic lymphocytic choriomeningitis virus (LCMV) infection in mice and we observed late clonal deletion of the KL25 cells. This process was governed by the binding affinity of the KL25 B cell receptor (BCR) to its target, the viral glycoprotein (GP), and the persistence of the antigen. We found that the loss of the KL25 B cells was independent of IFN-I inflammation, and it was the result of terminal differentiation into short-lived antibody secreting cells (ASCs). In a striking difference to antiviral T cells, long-term viremia did not result in a significantly altered transcriptional program in the LCMV- specific B cells compartment. The late deletion of high-affinity B cells in chronic infection may explain the delayed neutralizing antibody response to persistent pathogens. Strategies to counter B cell clonal deletion should help us improve humoral immunity against chronic infectious diseases.
Advisors:Pinschewer, Daniel
Committee Members:Jenal, Urs and Merkler, Doron
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer)
UniBasel Contributors:Pinschewer, Daniel and Jenal, Urs
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:15047
Thesis status:Complete
Number of Pages:146
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss150470
edoc DOI:
Last Modified:23 Jun 2023 04:30
Deposited On:22 Jun 2023 13:29

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