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Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect
- Source :
- The Journal of Experimental Medicine; July 2024, Vol. 221 Issue: 7 pe20221122-e20221122, 1p
- Publication Year :
- 2024
-
Abstract
- SYNTAXIN-11 (STX11) is a SNARE protein that mediates the fusion of cytotoxic granules with the plasma membrane at the immunological synapses of CD8 T or NK cells. Autosomal recessive inheritance of deleterious STX11 variants impairs cytotoxic granule exocytosis, causing familial hemophagocytic lymphohistiocytosis type 4 (FHL-4). In several FHL-4 patients, we also observed hypogammaglobulinemia, elevated frequencies of naive B cells, and increased double-negative DN2:DN1 B cell ratios, indicating a hitherto unrecognized role of STX11 in humoral immunity. Detailed analysis of Stx11-deficient mice revealed impaired CD4 T cell help for B cells, associated with disrupted germinal center formation, reduced isotype class switching, and low antibody avidity. Mechanistically, Stx11−/− CD4 T cells exhibit impaired membrane fusion leading to reduced CD107a and CD40L surface mobilization and diminished IL-2 and IL-10 secretion. Our findings highlight a critical role of STX11 in SNARE-mediated membrane trafficking and vesicle exocytosis in CD4 T cells, important for successful CD4 T cell–B cell interactions. Deficiency in STX11 impairs CD4 T cell–dependent B cell differentiation and humoral responses.
Details
- Language :
- English
- ISSN :
- 00221007 and 15409538
- Volume :
- 221
- Issue :
- 7
- Database :
- Supplemental Index
- Journal :
- The Journal of Experimental Medicine
- Publication Type :
- Periodical
- Accession number :
- ejs66315190
- Full Text :
- https://doi.org/10.1084/jem.20221122