Expression of the cytoplasmic tail of LMP1 in mice induces hyperactivation of B lymphocytes and disordered lymphoid architecture

Laura L Stunz; Lisa K Busch; Melissa E Munroe; Curt D Sigmund; Lorraine T Tygrett; Thomas J Waldschmidt; Gail A Bishop

doi:10.1016/j.immuni.2004.07.008

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Expression of the cytoplasmic tail of LMP1 in mice induces hyperactivation of B lymphocytes and disordered lymphoid architecture

Journal article

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Expression of the cytoplasmic tail of LMP1 in mice induces hyperactivation of B lymphocytes and disordered lymphoid architecture

Laura L Stunz, Lisa K Busch, Melissa E Munroe, Curt D Sigmund, Lorraine T Tygrett, Thomas J Waldschmidt and Gail A Bishop

Immunity (Cambridge, Mass.), Vol.21(2), pp.255-266

08/2004

DOI: 10.1016/j.immuni.2004.07.008

PMID: 15308105

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Abstract

The oncogenic EBV protein LMP1 mimics a dysregulated CD40 receptor in vitro. To compare CD40 and LMP1-mediated events in vivo, transgenic mice were engineered to express mouse CD40 (mCD40tg) or a protein with extracellular mCD40 and cytoplasmic LMP1 (mCD40-LMP1tg). Transgenic and CD40(-/-) mice were bred so that only the transgenic CD40 molecule is expressed in B cells, macrophages, and dendritic cells. mCD40-LMP1tg mice had normal lymphocyte subsets, and immunization elicited an antibody response featuring normal isotype switching, affinity maturation, and germinal center (GC) formation. However, unimmunized mCD40-LMP1tg mice had expanded immature and germinal center B cells, produced autoantibodies, exhibited marked splenomegaly and lymphadenopathy, and elevated serum IL-6. Thus, signaling through the LMP1 cytoplasmic tail results in amplified and abnormal mimicry of CD40 functions in vivo, indicating possible ways in which LMP1 contributes to the pathogenesis of EBV-associated human disease.

Spleen - immunology

Immunoglobulins - immunology

Hypersensitivity - immunology

Signal Transduction - immunology

Lymphocyte Activation - immunology

CD40 Antigens - metabolism

Epstein-Barr Virus Infections - etiology

Hypersensitivity - metabolism

Autoimmunity - immunology

Immunoglobulins - blood

Viral Matrix Proteins - metabolism

Interleukin-6 - metabolism

B-Lymphocytes - metabolism

Epstein-Barr Virus Infections - immunology

Spleen - cytology

Autoimmunity - physiology

Animals

B-Lymphocytes - immunology

Spleen - metabolism

Fluorescent Antibody Technique

Interleukin-6 - immunology

Antibody Formation

Mice

Viral Matrix Proteins - immunology

CD40 Antigens - immunology

Details

Title: Subtitle: Expression of the cytoplasmic tail of LMP1 in mice induces hyperactivation of B lymphocytes and disordered lymphoid architecture
Creators: Laura L Stunz - Department of Microbiology, Univeristy of Iowa, Iowa City, Iowa 52242, USA
Lisa K Busch
Melissa E Munroe
Curt D Sigmund
Lorraine T Tygrett
Thomas J Waldschmidt
Gail A Bishop
Resource Type: Journal article
Publication Details: Immunity (Cambridge, Mass.), Vol.21(2), pp.255-266
Publisher: United States
DOI: 10.1016/j.immuni.2004.07.008
PMID: 15308105
ISSN: 1074-7613
eISSN: 1097-4180
Grant note: CA09997 / NCI NIH HHS T32 AI007260 / NIAID NIH HHS
Language: English
Date published: 08/2004
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology; President; Pathology; Neuroscience and Pharmacology
Record Identifier: 9984001145902771

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