Engagement of CD153 (CD30 ligand) by CD30+ T cells inhibits class switch DNA recombination and antibody production in human IgD+ IgM+ B cells

Andrea Cerutti, Andràs Schaffer, Raymond G. Goodwin, Shefali Shah, Hong Zan, Scott Ely, Paolo Casali

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

CD153 (CD30 ligand) is a member of the TNF ligand/cytokine family expressed on the surface of human B cells. Upon exposure to IL-4, a critical Ig class switch-inducing cytokine, Ag-activated T cells express CD30, the CD153 receptor. The observation that dysregulated IgG, IgA, and/or IgE production is often associated with up-regulation of T cell CD30 prompted us to test the hypothesis that engagement of B cell CD153 by T cell CD30 modulates Ig class switching. In this study, we show that IgD+ IgM+ B cells up-regulate CD153 in the presence of CD154 (CD40 ligand), IL-4, and B cell Ag receptor engagement. In these cells, CD153 engagement by an agonistic anti- CD153 mAb or T cell CD30 inhibits Sμ→Sγ→, Sμ→Sα, and Sμ→Sε class switch DNA recombination (CSR). This inhibition is associated with decreased TNFR-associated factor-2 binding to CD40, decreased NF-κB binding to the CD40-responsive element of the Cγ3 promoter, decreased Iγ3-Cγ3 germline gene transcription, and decreased expression of Ku70, Ku80, DNA protein kinase, switch-associated protein-70, and Msh2 CSR-associated transcripts. In addition, CD153 engagement inhibits IgG, IgA, and IgE production, and this effect is associated with reduced levels of B lymphocyte maturation protein-1 transcripts, and increased binding of B cell-specific and activation protein to the Ig 3' enhancer. These findings suggest that CD30+ T cells modulate CSR as well as IgG, IgA, and IgE production by inducing reverse signaling through B cell CD153.

Original languageEnglish (US)
Pages (from-to)786-794
Number of pages9
JournalJournal of Immunology
Volume165
Issue number2
DOIs
StatePublished - Jul 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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