Molecular characterization of influenza-specific memory B cell subsets residing in human tissues

Abstract B cells can be divided into distinct subsets based on origin, activation history and functional attributes. Most human studies, which have characterized bulk polyclonal populations of circulating cells, suggest heterogeneity between the different cell subsets. Indeed, we showed that memory (Bmem) plasma from blood same donor exhibit patterns isotype distribution, mutational burden relatively limited clonal sharing. However, this may not extend to comparisons subset found within tissues or share reactivity. To test this, examined influenza hemagglutinin (HA)-specific Bmem in multiple donor-matched tissues. We first generated a high-throughput bead array displaying HAs seasonal (H1, H3) pandemic (H2, H5, H7, H9) flu strains screened serum >80 brain-dead tissue donors. All donors exhibited high IgG reactivity against strains. also identified some for are humans, suggesting these likely HA-specific potentially broadly reactive cross-reactive cells. directly identify with potential, enumerated H1 (CA09) H2 (NETH1999) specific by flow cytometry. show spleen whereas both present mediastinal lymph node (LN), mesenteric LN. The data repertoire HA differ Going forward, will characterize molecular signatures populations. Supported grants NIH (U19 AI142737,)