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,expa...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.展开更多
基金supported by the Deutsche Krebshilfe,Nr.70113859 to U.Z.-S.and H.A.,the Wilhelm-Sander-Stiftung Nr.2022.128.1 to A.Ö.Y and U.Z.-S.and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI170965。
文摘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.
