Modulation of a human lymphoblastoid B cell line by cyclic AMP. Ig secretion and phosphatidylcholine metabolism
A transformed human B cell line, LA350, was found to be sensitive to cAMP-elevating agents by responding with rapid (0 to 2 h) severalfold elevations of intracellular cAMP to treatment with cholera toxin, isobutylmethylxanthine (IBMX), forskolin, and dibutyryl cAMP (all p less than 0.001). These cAMP-elevating agents also produced significant inhibitions of subsequent (48 to 72 h) Ig secretion by the same B cells as measured by a reverse hemolytic plaque assay and an enzyme-linked immunoadsorbent assay for IgM (both p less than 0.001). PMA- and IBMX-treated cells were particularly responsive to the effects of cholera toxin, showing a doubling of cAMP content and profound decrease in Ig production (p less than 0.001). Because our previous studies had correlated activation of the metabolic turnover of the phosphatidylcholine (PC) fraction of membrane phospholipids with enhanced Ig secretion, we examined the sensitivity of PC metabolism to cAMP in control and PMA-stimulated cells. Formation of PC was found to be inhibited by forskolin and IBMX (both p less than 0.002) but breakdown of PC was stimulated (p less than 0.001). These findings imply that as the enzymatic products of PC, choline phosphate and diacylglycerol, are depleted due to the combined effects of cAMP upon synthesis and turnover of PC, there is a decrease in Ig secretion. Since diacylglycerol activates protein kinase C, it appears reasonable that Ig secretion is at least partially regulated by cAMP-responsive alterations in PC metabolism produced by protein kinase C-induced phosphorylation. We conclude that the early cAMP-sensitive changes in PC metabolism in this activated B cell line may signal for subsequent alterations in Ig secretion.
- Research Organization:
- Baylor College of Medicine, Houston, TX (USA)
- OSTI ID:
- 6744627
- Journal Information:
- J. Immunol.; (United States), Journal Name: J. Immunol.; (United States) Vol. 141:5; ISSN JOIMA
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
AMP
ANIMAL CELLS
ANTIGENS
AROMATICS
AZAARENES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
CHEMICAL REACTIONS
CHOLINE
CONNECTIVE TISSUE CELLS
DRUGS
ENZYME IMMUNOASSAY
ESTERS
GLOBULINS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IMMUNOASSAY
IMMUNOGLOBULINS
LEUKOCYTES
LIPIDS
LIPOTROPIC FACTORS
LYMPHOCYTES
MATERIALS
METABOLISM
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHORBOL ESTERS
PHOSPHOLIPIDS
PHOSPHORYLATION
PROTEINS
PURINES
QUATERNARY COMPOUNDS
SECRETION
SOMATIC CELLS
SYNTHESIS
TOXIC MATERIALS
TOXINS
XANTHINES