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| Status |
Public on Aug 26, 2020 |
| Title |
A CD4 T cell population expand and reshape autoreactive B cells, contributing to autoimmune lung pathology and post-infection autoimmunity in children |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Community acquired pneumonia (CAP) is a significant risk factor for autoimmune disease development. However, mechanisms underlying infection and autoimmunity remain elusive. Here, we report selective expansion of autoantibody producing CD21-CD19+ B cells by bronchoalveolar PD-1+CCR2+GZMA+RUNX3+ T helper 1 like (aTh1) cells in children with CAP. In bronchoalveolar lavage, the numbers of aTh1, CD21-B cells and the concentrations of IgG-specific autoantibodies correlated with CAP severity. Unexpectedly, PD-1 decreased the ability of CD21- B cells to produce autoantibodies and reshaped their specificity in the course of pathogen invasion. Nevertheless, respiratory infection induced aTh1 and CD21-B cell persistence may trigger autoimmune disease development in susceptible individuals; e.g. they were prevalent in cerebrospinal fluid of children with post-infection Guillain-Barre Syndrome. Thus, we reveal dual roles of aTh1 and CD21-B cells in infection immunity and autoimmune pathology, and demonstrate that PD-1 is a critical checkpoint inhibitor for autoimmune disease development.
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| Overall design |
The bronchoalveolar lavage fluid (BALF) samples from five patients were mixed and FACS-sorted as the following strategy. Briefly, the CD45+ fraction was retrieved and followed by depletion of CD14+ and CD16+ cells. The fractions of CD3E+ and CD3E- of the remaining cells were isolated for single-cell RNA sequencing. Human V(D)J+5’ Gene Expression product from 10X GENOMICS was used to measure paired gene expression and immune repertoire information (paired TCR or BCR) within single cells. By using Gel Beads-in-emulsion code (GEM-Code) technology, transcripts within each cell were indexed with unique barcode. After reverse transcription, the full-length cDNA was amplified via PCR with primers against common 5’ and 3’ ends added during GEM-RT. With sufficient starting material, the double stranded cDNA library was split into two subsamples for the construction of Single Cell 5’ expression and TCR- or BCR-enriched library, separately. The Single Cell V(D)J and 5’ Gene Expression libraries were sequenced at certain depth and running parameters.
**The approval process for the data release is pending from the Chinese Government***
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| Contributor(s) |
Lu B, Wang J, Chen Z, Yang D, Wang X, Zhan Y, Cui J, Lew AM, Lu L, Yang M, Lu G, Bai F, Zhang Y |
| Citation(s) |
32112047, 33772013 |
| Submission date |
Jan 09, 2019 |
| Last update date |
Apr 20, 2021 |
| Contact name |
Yuxia Zhang |
| E-mail(s) |
yuxia.zhang@gwcmc.org
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| Organization name |
Guangzhou Women and Children's Medical Center
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| Lab |
Zhang Lab
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| Street address |
9 Jinshui Rd, Tianhe District
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510510 |
| Country |
China |
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| Platforms (1) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA514084 |
| SRA |
SRP178225 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE124885_B_5prime_raw_gene_expression.csv.gz |
14.3 Mb |
(ftp)(http) |
CSV |
| GSE124885_B_5prime_vloupe_BCR.vloupe.tar.gz |
10.7 Mb |
(ftp)(http) |
TAR |
| GSE124885_B_5rime_normalized_gene_expression.csv.gz |
108.2 Mb |
(ftp)(http) |
CSV |
| GSE124885_T_5prime_normalized_gene_expression.csv.gz |
114.1 Mb |
(ftp)(http) |
CSV |
| GSE124885_T_5prime_raw_gene_expression.csv.gz |
14.7 Mb |
(ftp)(http) |
CSV |
| GSE124885_T_5prime_vloupe_TCR.vloupe.tar.gz |
37.3 Mb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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