 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 11, 2024 |
| Title |
B cells require DOCK8 to elicit and integrate T cell help when antigen is limiting |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
|
| Summary |
Dedicator of cytokinesis 8 (DOCK8) immunodeficiency syndrome is characterized by a failure of the germinal center response, a process involving the proliferation and positive selection of antigen-specific B cells. While DOCK8-deficient B cells are recruited into germinal centers, we find that they are arrested at a light-zone stage. They are unable to respond to T cell–dependent survival and selection signals, and consequently differentiate into plasma cells or memory B cells. Although DOCK8-deficient B cells can acquire and present antigen to initiate activation of cognate T cells, integrin upregulation, B–T cell conjugate formation, and costimulation are insufficient for sustained activation of B and T cells when antigen availability is limited. Our findings provide an explanation for the failure of B cell-dependent humoral responses in DOCK8 immunodeficiency syndrome, and offer insights into how the level of available antigen modulates B–T cell interactions necessary for humoral immune responses and immune memory.
|
| |
|
| Overall design |
Hen egg lysozyme (HEL)-specific splenic germinal centre (GC) B cells were sorted from mouse splenocytes on day 8 after adoptive transfer of splenic MD4 B cell mixtures and immunization with SRBC-HEL.
CD95+ HEL+ GC B cells from 6 spleens (3 from WT group, 3 from DOCK8-deficient group) were hashtagged (HTO labeled), pooled and sorted by flow cytometry into CD45.1+ (WT) or CD45.2+ (WT or DOCK8-deficient) subsets. The CD45.1 and CD45.2 multiplexed samples were processed independently on the 10X scRNASeq platform.
|
| |
|
| Contributor(s) |
Deobagkar-Lele M, Crawford G, Crockford TL, Back J, Hodgson R, Bhandari A, Bull KR, Cornall RJ |
| Citation(s) |
39121196 |
| |
| Submission date |
Jun 05, 2024 |
| Last update date |
Sep 10, 2024 |
| Contact name |
Mukta Deobagkar |
| Organization name |
University of Oxford
|
| Department |
Nuffield Department of Medicine
|
| Lab |
Cornall Lab
|
| Street address |
Centre for Human Genetics, Roosevelt Drive
|
| City |
Oxford |
| ZIP/Postal code |
OX3 7BN |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (4)
|
| GSM8306820 |
CD45.2 MD4 GC B cells, 838840_GX35 and 836436_GX35, GEX |
| GSM8306821 |
CD45.2 MD4 GC B cells, 838840_GX83 and 836436_GX83, HTO |
| GSM8306822 |
CD45.1 MD4 GC B cells, 838840_GX47 and 836436_GX47, GEX |
| GSM8306823 |
CD45.1 MD4 GC B cells, 838840_GX95 and 836436_GX95, HTO |
|
| Relations |
| BioProject |
PRJNA1120367 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE269130_HTO_antibodies_details.txt.gz |
314 b |
(ftp)(http) |
TXT |
| GSE269130_RAW.tar |
236.0 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...