Epstein-Barr virus and the B cell: a secret romance

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Epstein-Barr virus (EBV) primarily infects antigen-experienced memory B cells in immunocompetent individuals.
• Recent findings indicate EBV can also infect naive and germinal center (GC) B cells, particularly in post-transplant lymphoproliferative disease.
• Some EBV-positive B-cell clones exhibit non-functional Ig-V-region genes due to somatic mutations from GC reactions.

Purpose of the Study:

• To investigate the origin of EBV-infected B cells beyond memory B cells.
• To explore the implications of EBV infection on B cells with potentially deleterious mutations acquired during the GC reaction.
• To understand how EBV transformation might circumvent normal B-cell negative selection processes in GCs.

Main Methods:

• Analysis of B-cell populations in EBV-associated conditions.
• Genetic sequencing of Ig-V regions in EBV-positive B-cell clones.
• Comparative study of B-cell fate in the presence and absence of EBV infection.

Main Results:

• EBV infection is not limited to memory B cells and can involve naive and GC B cells.
• A subset of EBV-positive B-cell clones contains non-functional Ig-V-region genes.
• These mutations are acquired during the GC reaction, a process normally leading to apoptosis for faulty B cells.

Conclusions:

• EBV infection expands the repertoire of susceptible B-cell subsets.
• EBV transformation may provide a survival advantage to GC B cells with non-functional Ig-V genes.
• This suggests a mechanism by which EBV bypasses the negative selection checkpoints within germinal centers.