Abstract
Induction of resting B cell growth and differentiation requires a complex series of temporally coordinated signals that are initiated on contact with activated helper T cells. These signals complement one another, each rendering the B cell susceptible to factors supporting progressive activation. Here, we demonstrate that soluble CD14 (sCD14) bypasses the physiological sequelae of events that limit B cell activation. B cell growth and differentiation in vitro is induced by both native and recombinant forms of sCD14 at nanomolar concentrations. sCD14-mediated cellular activation does not require membrane CD14 expression, depends on a region of CD14 that is not involved in lipopolysaccharide binding, and requires functional Toll-like receptor 4. Consistent with biological activity of sCD14 in vitro, its administration to neonatal mice enhances Ig secretion. The results presented establish sCD14 as a naturally occurring soluble B cell mitogen of mammalian origin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Antibodies, Monoclonal / immunology
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Antibody Formation / drug effects*
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B-Lymphocytes / cytology
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B-Lymphocytes / drug effects*
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Cattle
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Cell Differentiation / drug effects
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Cell Division / drug effects
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Cells, Cultured / drug effects
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Colostrum / chemistry*
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Crosses, Genetic
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Culture Media, Serum-Free
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Drosophila Proteins*
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Humans
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Immunoglobulin Isotypes / blood
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Immunoglobulin M / blood
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Immunoglobulin kappa-Chains / blood
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Lipopolysaccharide Receptors / chemistry
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Lipopolysaccharide Receptors / immunology
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Lipopolysaccharide Receptors / isolation & purification
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Lipopolysaccharide Receptors / pharmacology*
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation / drug effects*
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Membrane Glycoproteins / drug effects
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Milk, Human / chemistry*
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Molecular Sequence Data
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Protein Structure, Tertiary
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Receptors, Cell Surface / drug effects
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Receptors, Cell Surface / physiology
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Recombinant Proteins / pharmacology
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Signal Transduction
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Solubility
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Spleen / cytology
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Toll-Like Receptor 4
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Toll-Like Receptors
Substances
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Antibodies, Monoclonal
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Culture Media, Serum-Free
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Drosophila Proteins
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Immunoglobulin Isotypes
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Immunoglobulin M
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Immunoglobulin kappa-Chains
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Lipopolysaccharide Receptors
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Lipopolysaccharides
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Membrane Glycoproteins
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Receptors, Cell Surface
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Recombinant Proteins
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TLR4 protein, human
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Toll-Like Receptor 4
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Toll-Like Receptors