Research Unit Gene Vectors, Research Group B-Cell Development and Activation, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany.
Institute of Asthma and Allergy Prevention, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Cell Mol Immunol. 2024 Dec;21(12):1410-1425. doi: 10.1038/s41423-024-01219-w. Epub 2024 Oct 17.
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.
最初，CD30 被鉴定为霍奇金淋巴瘤的标志物，随后在生发中心（GC）内和周围的一部分人类 B 细胞中检测到 CD30。虽然 CD30 表达通常局限于少数 B 细胞，但在某些免疫紊乱和病毒感染期间，CD30 表达的 B 细胞会扩增。CD30 在 B 细胞中的作用在很大程度上仍不清楚。为了解决这一知识空白，我们建立了一种条件性 CD30 敲入小鼠品系。在这些小鼠中，B 细胞特异性 CD30 表达导致年轻小鼠的 B 细胞表型正常，但大多数老年小鼠表现出 B 细胞、T 细胞和髓样细胞的显著扩增，以及 GC B 细胞和 IgG1 转换细胞的比例增加。这可能是由 CD4 衰老相关 T 细胞和滤泡辅助性 T 细胞的扩增驱动的，这些细胞部分表达 CD30-L（CD153），并可能刺激 CD30 表达的 B 细胞。在抗原激活的 B 细胞中诱导 CD30 表达可加速 GC 反应并增强浆细胞分化，可能通过 CXCR4 的转录后上调。此外，GC B 细胞中的 CD30 表达促进了 IgG1 转换细胞的扩增，这些细胞表现出 GC 或记忆样 B 细胞表型，与对照组相比，IgG1 水平异常升高。这些发现揭示了 CD30 信号在 GC B 细胞中的作用，并表明升高的 CD30 B 细胞数量导致病理性淋巴细胞激活和增殖。
