Outlining the Role of IgA in Memory Instruction – ORIgAMI

Influenza elicits robust immune responses upon infection, including the production of virus-specific antibodies of the immunoglobulin (Ig)M, IgG, and IgA isotypes. In particular, IgA plays a crucial role in protecting lung mucosal surfaces by neutralizing respiratory viruses and impeding their attachment to epithelial cells. Despite its protective role, we have very limited knowledge of the origin, selection and fate of B cells expressing an IgA B cell receptor (BCR) within germinal center reactions. In this frame, ORIgAMI (Origin and Role of IgA in Mucosal Immunity) will unveil if the IgA BCR:
- Imprints germinal center B cells with a specific transcriptional or epigenetic program.
- Differentially regulates antigen acquisition and selection within germinal center reactions.
- Bias germinal center B cells towards specific effector fates regardless of antigen affinity.
To unveil the dynamics of IgA+ B cells in germinal centers, we will use a respiratory infection model with influenza H1N1 virus, de novo-generated transgenic mice, multi-colour flow cytometry, single-cell RNA/ATAC-seq, high-resolution 3D imaging and DNA-based force sensors. A deep understanding of the biology of IgA-expressing B cells during respiratory viral infection is of fundamental interest and may provide clues towards the design of future vaccination approaches against air-borne pathogens.