Defining the origin and fate of human B cell responses to influenza virus vaccination.
Previous studies from our group has established that influenza vaccination of humans results in a transient burst of plasmablasts (or antibody secreting cells, ASCs) in peripheral blood (Figure 1). Afterwards, a subsequent wave of activated B cells (ABCs) emerges in blood and seed the memory B cell pool (Figure 1). Therefore, the dynamics and specificity of influenza vaccine induced B cell responses in blood are being thoroughly established. However, there remain major gaps in our current understanding of B cell responses to influenza virus vaccination in humans: (1) does influenza vaccination induce a GC reaction? (2) if yes, are all circulating ABCs GC derived? (3) if no, what is the phenotype of circulating GC derived B cells? 4) which GC-derived antigen-specific B cells are destined to become LLPCs? 5) does influenza vaccination induce a sustained increase in the frequency of bone marrow-resident LLPCs? 6) is there a correlation between the frequency of antigen-specific GC B cells or GC derived circulating ABCs and the increase/maintenance of bone marrow LLPCs? Tackling these gaps will allow us to discern the cellular and molecular determinants that are associated with durable antibody responses to vaccination in humans. In our laboratory, we employ a comprehensive approach that allows us to analyze antigen-specific B cell responses in the blood, draining lymph nodes as well as in the bone marrow after vaccination in humans. We directly and comprehensively interrogate B cell dynamics and the underlying molecular programs through the three major compartments which enable vaccine induced long-lasting humoral immune responses.
Figure 1. Bifurcation of B cell responses to infection and vaccination in humans (From Ellebedy AH Vaccines 2018)