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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 05, 2023 |
| Title |
The lipid Gb3 promotes germinal center B cell responses and anti-viral immunity |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
Influenza viruses escape immunity due to rapid antigenic evolution, which requires vaccination strategies that allow for broadly protective antibody responses. Here, we demonstrate that the lipid globotriaosylceramide (Gb3) expressed on germinal center (GC) B cells is essential for the production of high-affinity antibodies. Mechanistically, Gb3 binds and disengages CD19 from its chaperone CD81 for subsequent translocation to the B cell receptor (BCR) complex to trigger signaling. Moreover, this lipid regulates MHC-II expression to increase diversity of T follicular helper (Tfh) and GC B cells reactive with subdominant epitopes. In influenza infection, Gb3 promotes broadly reactive antibody responses and cross-protection. Thus, we show that Gb3 determines affinity as well as breadth in B cell immunity and propose this lipid as potential vaccine adjuvant against viral infection.
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| Overall design |
WT mouse germinal-center B cells (3 replicates)
Gla KO mouse germinal-center B cells (3 replicates)
A4galt KO mouse germinal-center B cells (3 replicates)
WT mouse naive B cells (3 replicates)
Gla KO mouse naive B cells (3 replicates)
A4galt KO mouse naive B cells (3 replicates)
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| Contributor(s) |
Sharma P, Zhang X, Ly K, Zhang Y, Hu Y, Ye AY, Hu J, Kim J, Lou M, Wang C, Celuzza Q, Kondo Y, Furukawa K, Bundle DR, Furukawa K, Alt FW, Winau F |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Nov 15, 2023 |
| Last update date |
Dec 06, 2023 |
| Contact name |
Frederick Alt |
| Organization name |
Boston Children's Hospital / Harvard Medical School
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| Department |
Program in Cellular and Molecular Medicine
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| Lab |
Frederick Alt
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| Street address |
1 Blackfan Circle
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
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| Samples (20)
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| GSM7900921 |
WT mouse germinal-center B cells BCR-seq rep1 |
| GSM7900922 |
WT mouse germinal-center B cells BCR-seq rep2 |
| GSM7900923 |
WT mouse germinal-center B cells BCR-seq rep3 |
| GSM7900924 |
Gla KO mouse germinal-center B cells BCR-seq rep1 |
| GSM7900925 |
Gla KO mouse germinal-center B cells BCR-seq rep2 |
| GSM7900926 |
Gla KO mouse germinal-center B cells BCR-seq rep3 |
| GSM7900927 |
A4galt KO mouse germinal-center B cells BCR-seq rep1 |
| GSM7900928 |
A4galt KO mouse germinal-center B cells BCR-seq rep2 |
| GSM7900929 |
A4galt KO mouse germinal-center B cells BCR-seq rep3 |
| GSM7900930 |
A4galt KO mouse germinal-center B cells BCR-seq rep4 |
| GSM7900931 |
WT mouse naive B cells BCR-seq rep1 |
| GSM7900932 |
WT mouse naive B cells BCR-seq rep2 |
| GSM7900933 |
WT mouse naive B cells BCR-seq rep3 |
| GSM7900934 |
Gla KO mouse naive B cells BCR-seq rep1 |
| GSM7900935 |
Gla KO mouse naive B cells BCR-seq rep2 |
| GSM7900936 |
Gla KO mouse naive B cells BCR-seq rep3 |
| GSM7900937 |
A4galt KO mouse naive B cells BCR-seq rep1 |
| GSM7900938 |
A4galt KO mouse naive B cells BCR-seq rep2 |
| GSM7900939 |
A4galt KO mouse naive B cells BCR-seq rep3 |
| GSM7900940 |
A4galt KO mouse naive B cells BCR-seq rep4 |
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| Relations |
| BioProject |
PRJNA1040498 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE247797_RAW.tar |
120.1 Mb |
(http)(custom) |
TAR (of XLS) |
SRA Run Selector |
| Raw data are available in SRA |
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