Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells
Name
148035.2-20210614134739-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf
Description
Published version
Size
1.51 MB
Format
Adobe PDF
Checksum (MD5)
304c4479b0454c7983238814276a14ee
Author(s)
Jiang, Ruoyi
Meng, Hailong
Raddassi, Khadir
Fleming, Ira
Hoehn, Kenneth B
Dardick, Kenneth R
Belperron, Alexia A
Montgomery, Ruth R
Shalek, Alex K
Hafler, David A
Date Issued
2021
Journal
JCI Insight
Publisher
American Society for Clinical Investigation
Citation
Jiang, Ruoyi, Meng, Hailong, Raddassi, Khadir, Fleming, Ira, Hoehn, Kenneth B et al. 2021. "Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells." JCI Insight, 6 (12).
Version
Final published version
Abstract
The skin lesion erythema migrans (EM) is an initial sign of the Ixodes tick-transmitted Borreliella spirochetal infection known as Lyme disease. T cells and innate immune cells have previously been shown to predominate the EM lesion and promote the reaction. Despite the established importance of B cells and antibodies in preventing infection, the role of B cells in the skin immune response to Borreliella is unknown. Here, we used single-cell RNA-Seq in conjunction with B cell receptor (BCR) sequencing to immunophenotype EM lesions and their associated B cells and BCR repertoires. We found that B cells were more abundant in EM in comparison with autologous uninvolved skin; many were clonally expanded and had circulating relatives. EM-associated B cells upregulated the expression of MHC class II genes and exhibited preferential IgM isotype usage. A subset also exhibited low levels of somatic hypermutation despite a gene expression profile consistent with memory B cells. Our study demonstrates that single-cell gene expression with paired BCR sequencing can be used to interrogate the sparse B cell populations in human skin and reveals that B cells in the skin infection site in early Lyme disease expressed a phenotype consistent with local antigen presentation and antibody production.
MIT Department
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1172/JCI.INSIGHT.148035
