Christoph Hafemeister and Florian Halbritter
St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria
Abstract
Secondary lymphoid organs (SLOs) provide the confined microenvironment required for stromal cells to interact with immune cells to initiate adaptive immune responses resulting in B-cell differentiation. Here, we studied three patients from two families with functional hyposplenism, absence of tonsils and complete lymph node aplasia, leading to recurrent bacterial and viral infections. We identified biallelic loss-of-function mutations in LTBR encoding the lymphotoxin beta receptor (LTβR), primarily expressed on stromal cells. LTβR-deficient patients had hypogammaglobulinemia, diminished memory B cells, regulatory and follicular T-helper cells, and dysregulated expression of several Tumor Necrosis Factor family members. B-cell differentiation in an ex vivo co-culture system was intact, implying that the observed B-cell defects were not intrinsic in nature, and instead result from LTβR-dependent stromal cell interaction signaling critical for SLO formation. Collectively, we define a human inborn error of immunity caused primarily by a stromal defect affecting the development and function of SLOs.
project.Dockerfiledefines the environment used to run the codeconfig.yamlis used to set pathsR/holds R function definitions and misc utility scriptsRmd/holds R markdown documents for the individual steps of the projectbash/holds shell scripts to build and run the docker image, and to parse the config file
The file knit.R calls all Rmd/*.Rmd files in order to reproduce the analysis.
Paths in the config.yaml file starting with "/path/to/" will have to be set.
Paper: Science Immunology, 22 Nov 2024, Vol 9, Issue 101, DOI: 10.1126/sciimmunol.adq8796
Data files: Raw data files are available at The European Genome-phenome Archive (EGA).