Polyclonal B cells acquire LCMV antigens in a GP1-dependent manner

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Hypergammaglobulinemia in murine models infected with Lymphocytic choriomeningitis virus (LCMV) is T-dependent.
• The mechanism of antigen acquisition by polyclonal B cells for presentation remains unclear.

Purpose of the Study:

• To investigate how polyclonal B cells acquire antigens for presentation during LCMV infection.
• To explore hypotheses regarding B cell antigen uptake mechanisms.

Main Methods:

• Utilized LCMV-specific CD4+ transgenic T cells to study B cell antigen uptake.
• Employed in vitro cell culture and in vivo mouse models.
• Transmission electron microscopy (TEM) to visualize viral particles.
• Used Fab fragments of LCMV-neutralizing antibody KL25.

Main Results:

• LCMV antigens from infected cells are accessible to polyclonal B cells in vitro, enabling T cell co-activation.
• Non-replicative LCMV allows B cell antigen acquisition, indicating productive infection is not required.
• B cells loaded with LCMV antigens in vitro can present them in vivo.
• TEM revealed LCMV-GP bearing particles <50nm, suggesting pinocytosis as an uptake mechanism.
• B cell antigen access is maintained despite inhibition of exosome or defective interfering particle release.
• Access to the viral GP1 protein is crucial for efficient B cell antigen acquisition.

Conclusions:

• Polyclonal B cells acquire LCMV antigens through pinocytosis of viral particles, independent of productive infection.
• The viral GP1 protein appears to be a key factor in B cell antigen uptake, suggesting a potential GP1 receptor on B cells.