Dysregulation of CD30+T cells by leukemia impairs isotype switching in normal B cells

Andrea Cerutti, Edmund C. Kim, Shefali Shah, Elaine J. Schattner, Hong Zan, András Schaffer, Paolo Casali

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Chronic lymphocytic leukemia (CLL) is associated with impaired immunoglobulin (Ig) class-switching from IgM to IgG and IgA, a defect that leads to recurrent infections.When activated in the presence of leukemic CLL B cells, T cells rapidly up-regulate CD30 through an OX40 ligand and interleukin 4 (IL-4)-dependent mechanism. These leukemia-induced CD30+ T cells inhibit CD40 ligand (CD40L)-mediated Sμ→Sγ and Sμ→Sα class-switch DNA recombination (CSR) by engaging CD30 ligand (CD30L), a molecule that interferes with the assembly of the CD40-tumor necrosis factor receptor-associated factor (TRAF) complex in nonmalignant IgD+ B cells. In addition, engagement of T cell CD30 by CD30L on neoplastic CLL B cells down-regulates the CD3-induced expression of CD40L. These findings indicate that, in CLL, abnormal CD30-CD30L interaction impairs IgG and IgA production by interfering with the CD40-mediated differentiation of nonmalignant B cells.

Original languageEnglish (US)
Pages (from-to)150-156
Number of pages7
JournalNature Immunology
Volume2
Issue number2
DOIs
StatePublished - Feb 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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