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Murine Model of CD40-activation of B cells
12:24

Murine Model of CD40-activation of B cells

Published on: March 5, 2010

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

A Cerutti1, E C Kim, S Shah

  • 1Division of Molecular Immunology, Department of Pathology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. acerutti@med.cornell.edu

Nature Immunology
|March 29, 2001
PubMed

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 S mu-->S gamma and S mu-->S alpha 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.

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