Abstract
Lupus disease is marked by B lymphocyte hyperactivity and the production of Abs to dsDNA. The production of these anti-dsDNA Abs is T lymphocyte dependent. However, it is not clear how CD4+ T lymphocytes provide help for B lymphocytes to produce IgG anti-dsDNA Abs. One possible mechanism is suggested by studies showing that human patients with systemic lupus erythematosus and lupus mice have increased numbers of CD40 ligand (CD40L)+ T and B lymphocytes. The results described in this study reveal that young, clinically healthy lupus-prone New Zealand Black x New Zealand White F1 (BWF1) mice have naive CD4+ T cells with preformed CD40L. These cells contribute to a brisk response to immunization and to the production of anti-dsDNA Abs. In vitro experiments revealed that CD4+ T cells with preformed CD40L could, upon stimulation, provide antiapoptotic signals for B cells but could not induce proliferation or reduce activation threshold. These results suggest that the direct target cells for the effect of T cells with preformed CD40L in lupus may not be B lymphocytes.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging / genetics
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Aging / immunology
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Animals
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Antibodies, Antinuclear / biosynthesis*
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Antibodies, Antinuclear / blood
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Antigens / administration & dosage
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Antigens / immunology
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / pathology
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CD40 Ligand / biosynthesis
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CD40 Ligand / immunology*
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Cell Aggregation / immunology
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Cell Differentiation / immunology
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Cell Division / genetics
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Cell Division / immunology
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Cell Survival / immunology
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Cells, Cultured
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Coculture Techniques
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Crosses, Genetic
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Cytoplasm / immunology
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Cytoplasm / metabolism
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DNA / immunology
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Genetic Predisposition to Disease*
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Immunization
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Immunophenotyping
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Kinetics
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Lupus Erythematosus, Systemic / genetics*
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Lupus Erythematosus, Systemic / immunology*
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Lupus Erythematosus, Systemic / pathology
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Lymphocyte Activation
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Lymphocyte Cooperation / immunology
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Lymphocyte Count
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Mice
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Mice, Inbred CBA
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Mice, Inbred NZB
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / pathology
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Antibodies, Antinuclear
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Antigens
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CD40 Ligand
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DNA