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

doi:10.1038/84254

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 journal › Article › peer-review

43 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 language	English (US)
Pages (from-to)	150-156
Number of pages	7
Journal	Nature Immunology
Volume	2
Issue number	2
DOIs	https://doi.org/10.1038/84254
State	Published - Feb 2001
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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@article{1478236962b94c1c8e2a6643070ff2ed,

title = "Dysregulation of CD30+T cells by leukemia impairs isotype switching in normal B cells",

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.",

author = "Andrea Cerutti and Kim, {Edmund C.} and Shefali Shah and Schattner, {Elaine J.} and Hong Zan and Andr{\'a}s Schaffer and Paolo Casali",

note = "Funding Information: Acknowledgements We are grateful to N. Chiorazzi for providing us with CLL samples. Supported by United States Public Health Service National Institutes of Health grants AI 45011,AG 13910 and AR40908 (to P. C.); an AIDS fellowship from the Istituto Superiore di Sanita (Rome, Italy) and a Career Development Award from the Systemic Lupus Erythematosus Foundation (to A. C.); a Cancer Research Institute Predoctoral Fellowship in Tumor Immunology (to A. S.); and a United States Public Health Service National Institutes of Health training grant in immunology T32 AI 07621 (to E. C. K.).",

year = "2001",

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doi = "10.1038/84254",

language = "English (US)",

volume = "2",

pages = "150--156",

journal = "Nature Immunology",

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AU - Cerutti, Andrea

AU - Kim, Edmund C.

AU - Shah, Shefali

AU - Schattner, Elaine J.

AU - Zan, Hong

AU - Schaffer, András

AU - Casali, Paolo

N1 - Funding Information: Acknowledgements We are grateful to N. Chiorazzi for providing us with CLL samples. Supported by United States Public Health Service National Institutes of Health grants AI 45011,AG 13910 and AR40908 (to P. C.); an AIDS fellowship from the Istituto Superiore di Sanita (Rome, Italy) and a Career Development Award from the Systemic Lupus Erythematosus Foundation (to A. C.); a Cancer Research Institute Predoctoral Fellowship in Tumor Immunology (to A. S.); and a United States Public Health Service National Institutes of Health training grant in immunology T32 AI 07621 (to E. C. K.).

PY - 2001/2

Y1 - 2001/2

N2 - 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.

AB - 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.

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

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