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| Status |
Public on Aug 09, 2024 |
| Title |
B cells targeting parasites capture spatially linked antigens to secure T cell help |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Our understanding of T-cell-dependent humoral responses has been largely shaped by studies involving model antigens such as recombinant proteins and viruses. In these contexts, B cells internalize the entire antigen or pathogen, and present a range of antigens to helper CD4+ T cells to initiate the humoral response. However, this model does not account for large pathogens (such as parasites) that are too large to be taken up by individual B cells, and the mechanisms by which B cells acquire and present antigens from large complex pathogens to T cells remain poorly understood. Here we used Plasmodium, the causative parasite of malaria, as a model to investigate the requirements for T cell help for B cells targeting the Plasmodium surface circumsporozoite protein (CSP). Upon Plasmodium sporozoite (SPZ) immunization, CSP-specific B cells can form a synapse-like structure with SPZs and take up CSP and non-CSP surface antigens. As a result, CSP-specific B cells can receive help from CD4+ T cells specific to antigens that are located on the surface but not cytosol of the Plasmodium SPZ. Therefore, B cells can obtain help, not only from T cells with the same protein specificity, but also from T cells specific for spatially linked antigens. This flexibility in T cell help may enhance the initiation and maintenance of humoral immune responses to complex pathogens.
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| Overall design |
MD4 mice were transferred with/without Ighg2A10 B cells, followed by rPfCSP-alum, PfCSP-SPZ immunization or left untreated, and spleens were collected 10 days post immunization. Tfh cells (CD4+CD44+PD-1+CXCR5+) were FACS-purified, hashtaged, counted and pooled (around 2000 cells per mice) for 10X scRNA-seq. Each sample has cells from 5 individual mice that are Hashtagged as 1-5. For sample 1, Hashtag1,2,3 : CSP1,2,3; Hashtag4,5: NoB1, NoB2. For sample2, Hashtag1,2,3: SPZ1,2,3; Hashtag4,5: UT1,2. More detailed information can be found at the R Markdown file associated with the paper at https://doi.org/10.6084/m9.figshare.26526313
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| Contributor(s) |
Gao X, Cockburn IA |
| Citation missing |
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| Submission date |
Aug 08, 2024 |
| Last update date |
Aug 09, 2024 |
| Contact name |
Xin Gao |
| E-mail(s) |
xin.gao@anu.edu.au
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| Phone |
0450031169
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| Organization name |
The Australian National University
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| Department |
Immunology
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| Street address |
131 Garran Rd
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| City |
Canberra |
| State/province |
ACT |
| ZIP/Postal code |
2601 |
| Country |
Australia |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1145999 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE274341_Sample1_Tfh_Processed_Resubmit.tar.gz |
127.8 Mb |
(ftp)(http) |
TAR |
| GSE274341_Sample2_Tfh_Processed_Resubmit.tar.gz |
265.5 Mb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
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