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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)
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords 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
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 1672-7681
Journal Cellular & Molecular Immunology
Publisher Nature Publishing Group
Publishing Place 5 Dongdan Santiao, Dongchen District, Being, 100005, Peoples R China
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
Institute of Asthma and Allergy Prevention (IAP)
Institute of Lung Health and Immunity (LHI)
Research Unit Molecular Immune Regulation (AMIR)
Institute of Virology (VIRO)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30202 - Environmental Health
Research field(s) Immune Response and Infection
Allergy
Lung Research
PSP Element(s) G-501500-003
G-503300-001
G-505000-007
G-501712-001
G-502710-001
G-501760-002
Grants National Institute of Allergy and Infectious Diseases of the National Institutes of Health
Wilhelm-Sander-Stiftung
Deutsche Krebshilfe
DOI 10.1038/s41423-024-01219-w
WOS ID 001334478900001
Scopus ID 85207245562
PubMed ID 39420111
Erfassungsdatum 2024-11-06
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