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B cells and progressive multifocal leukoencephalopathy: search for the missing link
Deniz Durali1, Marie-Ghislaine de Goër de Herve2, Jacques Gasnault2
1Immunology Research Laboratory, Department of Medical Microbiology, School of Medicine, Istanbul Medipol University , Istanbul , Turkey.
Frontiers in Immunology
|June 5, 2015
Summary
Progressive multifocal leukoencephalopathy (PML) is a fatal brain disease caused by JC virus (JCV). B cells play a key role in PML pathogenesis, potentially influencing T cell responses and JCV control.
Area of Science:
- Neuroimmunology
- Virology
- Immunology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the brain, primarily caused by JC virus (JCV) replication.
- PML is typically observed in severely immunocompromised individuals, with recent associations to therapeutic monoclonal antibodies like natalizumab and rituximab.
- Rituximab, a B cell-depleting antibody, has been linked to PML, highlighting the complex role of B cells in the disease.
Purpose of the Study:
- To elucidate the multifaceted role of B cells in the pathogenesis of Progressive multifocal leukoencephalopathy (PML).
- To investigate the potential of B cells as a viral reservoir and vector for JC virus (JCV) dissemination within the central nervous system.
- To explore how B cell immunomodulatory functions, particularly cytokine secretion, influence T cell responses and impact JCV infection control in PML, including rituximab-induced cases.
Main Methods:
- Review of existing literature on PML, JCV infection, and B cell immunobiology.
- Analysis of the proposed mechanisms of B cell involvement in JCV dissemination and central nervous system pathogenesis.
- Examination of the interplay between B cells, T cells, and cytokine secretion in the context of PML, with a focus on rituximab-associated cases.
Main Results:
- B cells may serve as a reservoir for JCV and facilitate its spread within the central nervous system.
- Anti-JCV antibody responses show limited efficacy in controlling viral replication within the brain.
- B cells significantly modulate T cell responses via cytokine secretion, impacting JCV infection and PML development.
Conclusions:
- B cells play a critical and complex role in the pathogenesis of Progressive multifocal leukoencephalopathy (PML).
- The immunomodulatory functions of B cells are crucial for controlling JC virus (JCV) infection and influence the development of PML, including rituximab-induced cases.
- Understanding B cell dynamics is essential for developing strategies to manage and prevent PML.
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