Robust B Cell Responses Predict Rapid Resolution of Lyme Disease

Abstract

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.

T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

“…Blum et al . identified preferential usage of certain IGHV segments in the plasmablast repertoires of Lyme disease patients. Tucci et al .…”

“…Similar V segment usage biases are also often found in repertoires of B-cell subpopulations. Blum et al [102] identified preferential usage of certain IGHV segments in the plasmablast repertoires of Lyme disease patients. Tucci et al [103] reported disrupted B-cell repertoires in a cohort of chronic HCV patients due to preferential usage of several IGHV segments in IGM memory B-cells.…”

Outer surface protein polymorphisms linked to host‐spirochete association in Lyme borreliae

“…The adaptive immune response also confers clearance of Lyme borreliae and may lead to clinical manifestations, such as arthritis. The B cell-mediated antibody immune response plays a major role for pathogen clearance (Steere and Glickstein, 2004;Blum et al, 2018). This B cell immunity is enhanced by B. burgdorferi-specific CD4 + T helper cell (T H 1) response, in which interferon-γ is the marker (Keane-Myers and Nickell, 1995; Kang et al, 1997;Zeidner et al, 1997).…”

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

“…One study that compared pre-and post-treatment serology in patients presenting with EM found that 39.4% of participants were seronegative at both timepoints [41]. Moreover, the magnitude and diversity of the B cell response to B. burgdorferi has been correlated to a faster resolution of clinical symptoms [42]; therefore, research that relies on adaptive immunity to classify patients according to serostatus could bias the sample toward less severe manifestations than those experienced by the broader Lyme population. For patients who do seroconvert, the conventional diagnostic paradigm is unable to discern past exposure from active infection, which is problematic for the clinician or researcher attempting to determine residual infection.…”