Zobrazit v EDS

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

Uloženo v:
Podrobná bibliografie
Název: CD30 influences germinal center B-cell dynamics and the expansion of IgG1-switched B cells
Autoři: Yan Wang, Ursula Rambold, Petra Fiedler, Tea Babushku, Claas L. Tapken, Kai P. Hoefig, Thomas P. Hofer, Heiko Adler, Ali Önder Yildirim, Lothar J. Strobl, Ursula Zimber-Strobl
Zdroj: Cell Mol Immunol
Informace o vydavateli: Springer Science and Business Media LLC, 2024.
Rok vydání: 2024
Témata: 631/250/2152/2153/1982, Cell Proliferation [MeSH], Mice, Inbred C57BL [MeSH], B-Lymphocytes/immunology [MeSH], Plasma Cells/immunology [MeSH], T Follicular Helper Cells/immunology [MeSH], CD30L, Cell Differentiation [MeSH], Animals [MeSH], Germinal Center/immunology [MeSH], Lymphocyte Activation [MeSH], Senescence associated T cells (SAT cells), Immunoglobulin G/immunology [MeSH], Mice [MeSH], Article, B lymphocytes, Ki-1 Antigen/metabolism [MeSH], CD30, Germinal center reaction, 631/250/1619/40, Conditional mice, Immunoglobulin Class Switching [MeSH], Receptors, CXCR4/metabolism [MeSH], article, B-Lymphocytes, Receptors, CXCR4, T Follicular Helper Cells, Plasma Cells, Ki-1 Antigen, Cell Differentiation, Germinal Center, Lymphocyte Activation, Immunoglobulin Class Switching, Mice, Inbred C57BL, Mice, Immunoglobulin G, Animals, Cell Proliferation
Popis: 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.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 2042-0226
DOI: 10.1038/s41423-024-01219-w
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/39420111
https://repository.publisso.de/resource/frl:6492539
Rights: CC BY
Přístupové číslo: edsair.doi.dedup.....5177dfcc903876ca5af182f5402abe95
Databáze: OpenAIRE
Popis
Abstrakt: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.
ISSN:20420226
DOI:10.1038/s41423-024-01219-w