Science and Research

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

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.

  • Wang, Y.
  • Rambold, U.
  • Fiedler, P.
  • Babushku, T.
  • Tapken, C. L.
  • Hoefig, K. P.
  • Hofer, T. P.
  • Adler, H.
  • Yildirim, AÖ
  • Strobl, L. J.
  • Zimber-Strobl, U.

Keywords

  • B lymphocytes
  • Cd30
  • Cd30l
  • Conditional mice
  • Germinal center reaction
  • Senescence associated T cells (SAT cells)
Publication details
DOI: 10.1038/s41423-024-01219-w
Journal: Cell Mol Immunol
Work Type: Original
Location: CPC-M
Disease Area: AA
Partner / Member: HMGU
Access-Number: 39420111

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