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CD30 influences germinal center B-cell dynamics and the expansion of IgG1-switched B cells.

Cell. Mol. Immunol., DOI: 10.1038/s41423-024-01219-w (2024)
Verlagsversion DOI PMC
Open Access Hybrid
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Initially, identified as a Hodgkin lymphoma marker, CD30 was subsequently detected on a subset of human B cells within and around germinal centers (GCs). While CD30 expression is typically restricted to a few B cells, expansion of CD30-expressing B cells occurs in certain immune disorders and during viral infections. The role of CD30 in B cells remains largely unclear. To address this gap in knowledge, we established a conditional CD30-knockin mouse strain. In these mice, B-cell-specific CD30 expression led to a normal B-cell phenotype in young mice, but most aged mice exhibited significant expansion of B cells, T cells and myeloid cells and increased percentages of GC B cells and IgG1-switched cells. This may be driven by the expansion of CD4+ senescence-associated T cells and T follicular helper cells, which partially express CD30-L (CD153) and may stimulate CD30-expressing B cells. Inducing CD30 expression in antigen-activated B cells accelerates the GC reaction and augments plasma cell differentiation, possibly through the posttranscriptional upregulation of CXCR4. Furthermore, CD30 expression in GC B cells promoted the expansion of IgG1-switched cells, which displayed either a GC or memory-like B-cell phenotype, with abnormally high IgG1 levels compared with those in controls. These findings shed light on the role of CD30 signaling in GC B cells and suggest that elevated CD30+ B-cell numbers lead to pathological lymphocyte activation and proliferation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter B Lymphocytes ; Cd30 ; Cd30l ; Conditional Mice ; Germinal Center Reaction ; Senescence Associated T Cells (sat Cells); Antibody-responses; T-cells; Expression; Receptor; Population; Selection; Lymphoma; Antigen; Cxcr4; Nuclear
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 1672-7681
Verlag Nature Publishing Group
Verlagsort 5 Dongdan Santiao, Dongchen District, Being, 100005, Peoples R China
Begutachtungsstatus Peer reviewed
POF Topic(s) 30203 - Molecular Targets and Therapies
30202 - Environmental Health
Forschungsfeld(er) Immune Response and Infection
Allergy
Lung Research
PSP-Element(e) G-501500-003
G-503300-001
G-505000-007
G-501712-001
G-502710-001
G-501760-002
Förderungen National Institute of Allergy and Infectious Diseases of the National Institutes of Health
Wilhelm-Sander-Stiftung
Deutsche Krebshilfe
Scopus ID 85207245562
PubMed ID 39420111
Erfassungsdatum 2024-11-06