ArticleBlood2021
Hematologic disorder-associated Cxcr4 gain-of-function mutation leads to uncontrolled extrafollicular immune response.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Case Report: Functional characterization of lymphocyte populations in a pediatric patient with WHIM syndrome.Frontiers in immunology · 2026Article
- Analysis and Interpretation of Somatic NMD-Escaping Variants in Oncogenes and Dual-Function Genes across Adult and Pediatric Cancer Cohorts.medRxiv : the preprint server for health sciences · 2025Article
- Neurodevelopmental origins of structural and psychomotor defects in CXCR4-linked primary immunodeficiency.Neuron · 2025Article
- Review
- CD30 influences germinal center B-cell dynamics and the expansion of IgG1-switched B cells.Cellular & molecular immunology · 2024Article
- Estimate the relationship between CXCR4-SDF-1 axis and inhibitory molecules (CTLA4 and PD-1) in patients with colon cancer.Narra J · 2024Article
- CXCR4 signaling determines the fate of hematopoietic multipotent progenitors by stimulating mTOR activity and mitochondrial metabolism.Science signaling · 2024Article
- Mitochondria Activity and CXCR4 Collaboratively Promote the Differentiation of CD11cImmune network · 2024Article
- Plerixafor for pathogen-agnostic treatment in murine thigh infection and zebrafish sepsis.Clinical and translational science · 2024Article
- CXCR4: from B-cell development to B cell-mediated diseases.Life science alliance · 2024Review
- WHIM Syndrome-linked CXCR4 mutations drive osteoporosis.Nature communications · 2023Article
- Sec22b is a critical and nonredundant regulator of plasma cell maintenance.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- In good times and in bad: How plasma cells resolve stress for a life-long union with the bone marrow.Frontiers in immunology · 2023Article
- An Extended Prognostic Index of the ISSWM Score Based on Thyroid Complications in Waldenström Macroglobulinemia/Lymphoplasmacytoid Lymphoma.Frontiers in oncology · 2022Article
- Article
- Hematopoietic Multipotent Progenitors and Plasma Cells: Neighbors or Roommates in the Mouse Bone Marrow Ecosystem?Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The extrafollicular immune response is essential to generate a rapid but transient wave of protective antibodies during infection. Despite its importance, the molecular mechanisms controlling this first response are poorly understood. Here, we demonstrate that enhanced Cxcr4 signaling caused by defective receptor desensitization leads to exacerbated extrafollicular B-cell response. Using a mouse model bearing a gain-of-function mutation of Cxcr4 described in 2 human hematologic disorders, warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome and Waldenström macroglobulinemia, we demonstrated that mutant B cells exhibited enhanced mechanistic target of rapamycin signaling, cycled more, and differentiated more potently into plasma cells than wild-type B cells after Toll-like receptor (TLR) stimulation. Moreover, Cxcr4 gain of function promoted enhanced homing and persistence of immature plasma cells in the bone marrow, a phenomenon recapitulated in WHIM syndrome patient samples. This translated in increased and more sustained production of antibodies after T-independent immunization in Cxcr4 mutant mice. Thus, our results establish that fine-tuning of Cxcr4 signaling is essential to limit the strength and length of the extrafollicular immune response.
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Registered trials
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