Regulation of surface IgM- and IgD-mediated inositol phosphate formation and Ca2+ mobilization in murine B lymphocytes.
Cross-linking of surface IgM or IgD receptors on B cells initiates a signaling cascade involving the activation of an (uncharacterized) G-protein: this in turn activates a polyphosphoinositide-specific phosphodiesterase (PPI-PDE), thereby leading to the release of inositol phosphates. In order to investigate if the two isotypes of sIg share a common G-protein, we stimulated B cells sequentially with anti-mu and anti-delta antibodies. Ligation of either class of receptor for 1 h led to the activation of the PPI-PDE, which persisted for several hours. However, this was accompanied by inhibition of further stimulation of the enzyme via the heterologous receptors. This desensitization was shown to operate at the level of the coupling between G-protein and the PPI-PDE. These effects waned after 4-8 h of stimulation, when signaling via the heterologous receptors had essentially returned to normal. In addition, stimulation of B cells by anti-mu and anti-delta together did not elicit additive responses, either in terms of increases in inositol phosphate production, or in terms of increases in intracellular Ca2+ levels. Taken together, these results indicate that sIgM and IgD receptors share a common G-protein and that signaling via these receptors is under both positive and negative feedback control. The mechanisms involved are unknown, but these effects may well be due to modulation of the activities of components of the signaling cascade by protein kinase C.
Harnett
M M
MM
Division of Immunology, National Institute for Medical Research, Mill Hill, London.
Holman
M J
MJ
Klaus
G G
GG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000494:pharmacology; D007072:Immunoglobulin D / Q000032:analysis / Q000502:physiology*; D007075:Immunoglobulin M / Q000032:analysis / Q000502:physiology*; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D013873:Thionucleotides / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007295:Inositol Phosphates; D011947:Receptors, Antigen, B-Cell; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D002118:Calcium