|
| Status |
Public on Jun 07, 2021 |
| Title |
Single Cell Immunophenotyping of Lyme Erythema Migrans Identifies IgM-Switched Memory B Cells (10X Single-Cell Gene Expression) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Erythema migrans (EM) is a skin lesion caused by the spirochete B. burgdorferi (Bb) and is a hallmark initial sign of Lyme disease. Previous studies have demonstrated that T cells and innate immune cells mediate local inflammatory cytokine production that promote the reaction. Despite the established importance of B cells and antibodies in preventing Bb infection and resolving disease, the role of B cells in the skin immune response to Bb is incompletely defined. In this study, we characterized the immunophenotype of EM lesions and used single cell RNA-Seq to investigate B cell receptor (BCR) and T cell receptor (TCR) repertoires in the EM skin lesions and peripheral blood of patients with Lyme disease. We hypothesized that B cells from the circulation, potentially primed by exposure to Bb antigens in regional draining lymph nodes, are recruited into EM lesions and play an active role in the local response to infection. We found that B cells are more abundant in the EM lesion in comparison to autologous uninvolved skin and possess distinct characteristics, including abundant expression of MHCII genes and preferential IgM isotype usage. A subset exhibited low levels of somatic hypermutation despite a gene expression profile more consistent with memory than naïve B cell subsets. Moreover, infiltrating B cells were clonally expanded and a large fraction could be directly traced to circulating relatives. By leveraging single cell gene expression with paired BCR and TCR repertoire sequencing, we demonstrate, for the first time, that B cells are recruited to the skin infection site in early Lyme disease and express a phenotype suggesting that they could play a role in local antigen presentation and antibody production.
|
| |
|
| Overall design |
Six subjects were studied, all with confirmed cases of Lyme Disease. Five of six had samples from both EM rash and unaffected skin. One subject had sample only from EM rash. One subject had an additional PBMC sample.
|
| |
|
| Contributor(s) |
Melillo T, Jiang R, Meng H, Kleinstein SH, Bockenstedt LK |
| Citation(s) |
34061047 |
| BioProject |
PRJNA701454 |
| Submission date |
Feb 15, 2021 |
| Last update date |
Mar 16, 2023 |
| Contact name |
Steven Kleinstein |
| Organization name |
Yale University
|
| Department |
Pathology
|
| Lab |
Kleinstein
|
| Street address |
300 George St.
|
| City |
New Haven |
| State/province |
Ct |
| ZIP/Postal code |
06511 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (12)
|
|
| This SubSeries is part of SuperSeries: |
| GSE169440 |
Single Cell Immunophenotyping of Lyme Erythema Migrans |
|
Less...
More...