AUTHOR=Blum Lisa K. , Adamska Julia Z. , Martin Dale S. , Rebman Alison W. , Elliott Serra E. , Cao Richard R. L. , Embers Monica E. , Aucott John N. , Soloski Mark J. , Robinson William H. 

TITLE=Robust B Cell Responses Predict Rapid Resolution of Lyme Disease

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01634

DOI=10.3389/fimmu.2018.01634

ISSN=1664-3224

ABSTRACT=<p>Lyme disease (<italic>Borrelia burgdorferi</italic> infection) is increasingly recognized as a significant source of morbidity worldwide. Here, we show that blood plasmablasts and CD27<sup>−</sup> memory B cells are elevated in untreated Lyme disease, with higher plasmablast levels associated with more rapid resolution of clinical symptoms. Stronger serum reactivity to surface proteins and peptides from <italic>B. burgdorferi</italic> was also associated with faster resolution of clinical symptoms. Through molecular identifier-enabled antibody heavy-chain sequencing of bulk B cells and single-cell paired-chain antibody sequencing of blood plasmablasts, we characterized immunoglobulin gene usage patterns specific to <italic>B. burgdorferi</italic> infection. Recombinantly expressed antibodies from expanded lineages bound <italic>B. burgdorferi</italic> antigens, confirming that these clones are driven by the infection. Furthermore, recombinant sequence-derived antibodies were functional, inhibiting growth of <italic>B. burgdorferi in vitro</italic>. Elevations and clonal expansion of blood plasmablasts were associated with rapid return to health, while poor plasmablast responses were associated with a longer duration of symptoms following treatment. Plasmablasts induced by <italic>B. burgdorferi</italic> infection showed preferential antibody gene segment usage, while bulk sequencing of total B cells revealed convergent CDR3 motifs specific to <italic>B. burgdorferi</italic>-infected patients. Our results show that robust plasmablast responses encoding <italic>Bb</italic>-static antibodies are associated with more rapid resolution of Lyme disease, and these antibodies could provide the basis for next-generation therapeutics for Lyme disease.</p>