Wang, Y. ; Rambold, U. ; Fiedler, P. ; Babushku, T. ; Tapken, C.L. ; Hoefig, K.P. ; Hofer, T.P. ; Adler, H. ; Yildirim, A.Ö. ; Strobl, L.J. ; Zimber-Strobl, U.
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)
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
Typ der Hochschulschrift
Herausgeber
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
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2024
Prepublished im Jahr
0
HGF-Berichtsjahr
2024
ISSN (print) / ISBN
1672-7681
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Nature Publishing Group
Verlagsort
5 Dongdan Santiao, Dongchen District, Being, 100005, Peoples R China
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0000-00-00
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0000-00-00
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0000-00-00
Anmelder/Inhaber
weitere Inhaber
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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
Copyright
Erfassungsdatum
2024-11-06