Robust B Cell Responses Predict Rapid Resolution of Lyme Disease
Lyme disease (Borrelia burgdorferi infection) is increasingly recognized as a significant source of morbidity worldwide. Here, we show that blood plasmablasts and CD27− memory B cells are elevated in untreated Lyme disease, with higher plasmablast levels associated with more rapid resolution of clin...
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doaj-8fd9a2dc94fb4e1fac9968907af1f97a2020-11-24T23:29:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-07-01910.3389/fimmu.2018.01634387241Robust B Cell Responses Predict Rapid Resolution of Lyme DiseaseLisa K. Blum0Lisa K. Blum1Julia Z. Adamska2Julia Z. Adamska3Dale S. Martin4Alison W. Rebman5Serra E. Elliott6Serra E. Elliott7Richard R. L. Cao8Monica E. Embers9John N. Aucott10Mark J. Soloski11William H. Robinson12William H. Robinson13Stanford University School of Medicine, Stanford, CA, United StatesVA Palo Alto Healthcare System, Palo Alto, CA, United StatesStanford University School of Medicine, Stanford, CA, United StatesVA Palo Alto Healthcare System, Palo Alto, CA, United StatesDivision of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA, United StatesLyme Disease Research Center, Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesStanford University School of Medicine, Stanford, CA, United StatesVA Palo Alto Healthcare System, Palo Alto, CA, United StatesStanford University School of Medicine, Stanford, CA, United StatesDivision of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA, United StatesLyme Disease Research Center, Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesLyme Disease Research Center, Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesStanford University School of Medicine, Stanford, CA, United StatesVA Palo Alto Healthcare System, Palo Alto, CA, United StatesLyme disease (Borrelia burgdorferi infection) is increasingly recognized as a significant source of morbidity worldwide. Here, we show that blood plasmablasts and CD27− 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 B. burgdorferi 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 B. burgdorferi infection. Recombinantly expressed antibodies from expanded lineages bound B. burgdorferi antigens, confirming that these clones are driven by the infection. Furthermore, recombinant sequence-derived antibodies were functional, inhibiting growth of B. burgdorferi in vitro. 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 B. burgdorferi infection showed preferential antibody gene segment usage, while bulk sequencing of total B cells revealed convergent CDR3 motifs specific to B. burgdorferi-infected patients. Our results show that robust plasmablast responses encoding Bb-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.https://www.frontiersin.org/article/10.3389/fimmu.2018.01634/fullLyme diseaseBorreliaantibodiesplasmablastsimmune repertoire |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lisa K. Blum Lisa K. Blum Julia Z. Adamska Julia Z. Adamska Dale S. Martin Alison W. Rebman Serra E. Elliott Serra E. Elliott Richard R. L. Cao Monica E. Embers John N. Aucott Mark J. Soloski William H. Robinson William H. Robinson |
spellingShingle |
Lisa K. Blum Lisa K. Blum Julia Z. Adamska Julia Z. Adamska Dale S. Martin Alison W. Rebman Serra E. Elliott Serra E. Elliott Richard R. L. Cao Monica E. Embers John N. Aucott Mark J. Soloski William H. Robinson William H. Robinson Robust B Cell Responses Predict Rapid Resolution of Lyme Disease Frontiers in Immunology Lyme disease Borrelia antibodies plasmablasts immune repertoire |
author_facet |
Lisa K. Blum Lisa K. Blum Julia Z. Adamska Julia Z. Adamska Dale S. Martin Alison W. Rebman Serra E. Elliott Serra E. Elliott Richard R. L. Cao Monica E. Embers John N. Aucott Mark J. Soloski William H. Robinson William H. Robinson |
author_sort |
Lisa K. Blum |
title |
Robust B Cell Responses Predict Rapid Resolution of Lyme Disease |
title_short |
Robust B Cell Responses Predict Rapid Resolution of Lyme Disease |
title_full |
Robust B Cell Responses Predict Rapid Resolution of Lyme Disease |
title_fullStr |
Robust B Cell Responses Predict Rapid Resolution of Lyme Disease |
title_full_unstemmed |
Robust B Cell Responses Predict Rapid Resolution of Lyme Disease |
title_sort |
robust b cell responses predict rapid resolution of lyme disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-07-01 |
description |
Lyme disease (Borrelia burgdorferi infection) is increasingly recognized as a significant source of morbidity worldwide. Here, we show that blood plasmablasts and CD27− 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 B. burgdorferi 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 B. burgdorferi infection. Recombinantly expressed antibodies from expanded lineages bound B. burgdorferi antigens, confirming that these clones are driven by the infection. Furthermore, recombinant sequence-derived antibodies were functional, inhibiting growth of B. burgdorferi in vitro. 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 B. burgdorferi infection showed preferential antibody gene segment usage, while bulk sequencing of total B cells revealed convergent CDR3 motifs specific to B. burgdorferi-infected patients. Our results show that robust plasmablast responses encoding Bb-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. |
topic |
Lyme disease Borrelia antibodies plasmablasts immune repertoire |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.01634/full |
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