Influenza-specific memory B cells in the mucosa - differentiation, specificity and protective role

B cell and antibody (Abs) are crucial for our protection against viral infection and re-infection.

The first site of entry for respiratory viruses, such as influenza A virus (IAV), is the upper respiratory tract (URT) mucosa followed by viral proliferation in the lungs. Surprisingly, almost nothing is known about memory B cells (Bmem) that reside in mucosal tissues.

A detailed understanding of their origin, specificity and ability to differentiate upon reinfection is a crucial first step in designing targeted vaccines and adjuvants.In our previous study we have discovered that a large number of Bmem develop in the lymph nodes after infection and subsequently migrate to the lungs where they assume residency.

Here we will study the development and maintenance of such cells in lungs and URT and derive crucial information on their protective role.In detail we will: 1) Determine which factors contribute to migration, development and maintenance of lung-resident Bmem. 2) Define epitope-specificity and clonal relationship of resident Bmem in URT vs lungs and their relative ability to differentiate in Ab-secreting plasma cells and their role in protection. 3) Use CRISPR/Cas9 engineering of B cell receptor to follow fate decision of broadly neutralizing B cells, of defined specificity.Overall, this project will generate unprecedented insights into the differentiation, specificity and protective role of Bmem.

This is an important step in developing targeted vaccinations and adjuvants.