Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells
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 c...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2022
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| Online Access: | https://hdl.handle.net/1721.1/141303 |
| _version_ | 1811070397170319360 |
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| author | 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 Kleinstein, Steven H Bockenstedt, Linda K |
| author2 | Ragon Institute of MGH, MIT and Harvard |
| author_facet | Ragon Institute of MGH, MIT and Harvard 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 Kleinstein, Steven H Bockenstedt, Linda K |
| author_sort | Jiang, Ruoyi |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:35:19Z |
| format | Article |
| id | mit-1721.1/141303 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:35:19Z |
| publishDate | 2022 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | mit-1721.1/1413032024-03-19T17:32:34Z Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells 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 Kleinstein, Steven H Bockenstedt, Linda K 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 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. 2022-03-18T18:20:01Z 2022-03-18T18:20:01Z 2021 2022-03-18T18:17:17Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141303 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). en 10.1172/JCI.INSIGHT.148035 JCI Insight Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf American Society for Clinical Investigation American Society for Clinical Investigation |
| spellingShingle | 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 Kleinstein, Steven H Bockenstedt, Linda K Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells |
| title | Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells |
| title_full | Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells |
| title_fullStr | Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells |
| title_full_unstemmed | Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells |
| title_short | Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells |
| title_sort | single cell immunophenotyping of the skin lesion erythema migrans identifies igm memory b cells |
| url | https://hdl.handle.net/1721.1/141303 |
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