Abstract
Production of nerve growth factor (NGF) was assessed in cultures of human T and B lymphocytes and macrophages. NGF was constitutively produced by B cells only, which also expressed surface p140trk-A and p75NGFR molecules and hence efficiently bound and internalized the cytokine. Neutralization of endogenous NGF caused disappearance of Bcl-2 protein and apoptotic death of resting lymphocytes bearing surface IgG or IgA, a population comprising memory cells, while surface IgM/IgD "virgin" B lymphocytes were not affected. In vivo administration of neutralizing anti-NGF antibodies caused strong reduction in the titer of specific IgG in mice immunized with tetanus toxoid, nitrophenol, or arsonate and reduced numbers of surface IgG or IgA B lymphocytes. Thus, NGF is an autocrine survival factor for memory B lymphocytes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody Specificity
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B-Lymphocyte Subsets / chemistry
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B-Lymphocyte Subsets / cytology
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B-Lymphocyte Subsets / metabolism*
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Cell Survival / immunology
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Cells, Cultured / chemistry
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Cells, Cultured / cytology
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Cells, Cultured / metabolism
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Female
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Humans
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Immunologic Memory / immunology*
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Immunophenotyping
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Mice
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Mice, Inbred BALB C
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Nerve Growth Factors / biosynthesis*
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Nerve Growth Factors / immunology
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Nerve Growth Factors / metabolism
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Neutralization Tests
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / physiology
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Receptor Protein-Tyrosine Kinases / biosynthesis
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Receptor Protein-Tyrosine Kinases / physiology
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Receptor, trkA
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Receptors, Cell Surface / analysis
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Receptors, Nerve Growth Factor / biosynthesis
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Receptors, Nerve Growth Factor / physiology
Substances
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Nerve Growth Factors
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Proto-Oncogene Proteins
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Receptors, Cell Surface
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Receptors, Nerve Growth Factor
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Receptor Protein-Tyrosine Kinases
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Receptor, trkA