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B cells require DOCK8 to elicit and integrate T cell help when antigen is limiting

GSE269130 Mus musculus Expression profiling by high throughput sequencing; Other 4 samples Submitted 2024/06/11 Platform GPL24247
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.
Published in
B cells require DOCK8 to elicit and integrate T cell help when antigen is limiting
Deobagkar-Lele M, Crawford G, Crockford TL et al. · Science immunology 2024 · PMID 39121196 · doi:10.1126/sciimmunol.add4874
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Also filed as BioProject PRJNA1120367 and SRA study SRP511954. Searching any of these in the dataset finder brings you back here.

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