Antagonistic roles for phospholipase D activities in B cell signaling: while the antigen receptors transduce mitogenic signals via a novel phospholipase D activity, phosphatidylcholine-phospholipase D mediates antiproliferative signals.
Cross-linking of the Ag receptors on B cells induces DNA synthesis and proliferation. Butanol trap experiments suggest that one or more phospholipase D activities play a key role in this process. Although phosphatidylcholine-phospholipase D has been shown to play a central role in the transduction of proliferative responses for a wide variety of calcium-mobilizing receptors, we show that the Ag receptors are not coupled to this phospholipase. In addition, phosphatidylcholine-phospholipase D is not stimulated under conditions that mimic T cell-dependent B cell activation. In contrast, ATP, which inhibits surface Ig (sIg)-mediated DNA synthesis in murine B cells via P2-purinoceptors, activates phosphatidylcholine-phospholipase D. Phosphatidylcholine-phospholipase D is therefore associated with antiproliferative signal transduction in mature B cells, but it does not transduce early signals associated with sIg-mediated growth arrest or apoptosis in immature B cells. Mitogenic stimulation of sIg is, however, coupled to a novel nonphosphatidylcholine-hydrolyzing phospholipase D activity. The resultant sIg-generated phosphatidic acid, unlike the phosphatidylcholine-derived phosphatidic acid generated via the purinoceptors, is converted to diacylglycerol. These data provide the first evidence that while the novel sIg-coupled phospholipase D and resultant diacylglycerol generation may play a role in B cell survival and proliferation, phosphatidylcholine-phospholipase D may transduce, via phosphatidic acid, negative immunomodulatory signals in mature B lymphocytes.
Gilbert
J J
JJ
Department of Immunology, University of Glasgow, Scotland.
Pettitt
T R
TR
Seatter
S D
SD
Reid
S D
SD
Wakelam
M J
MJ
Harnett
M M
MM
D020001:1-Butanol / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division; D002460:Cell Line; D004261:DNA Replication; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000502:physiology*; D008055:Lipids / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D010739:Phospholipase D / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D007527:Isoenzymes; D008055:Lipids; D008070:Lipopolysaccharides; D008563:Membrane Lipids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D011947:Receptors, Antigen, B-Cell; D000255:Adenosine Triphosphate; D020001:1-Butanol; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate