Signaling events during helper T cell-dependent B cell activation. I. Analysis of the signal transduction pathways triggered by activated helper T cell in resting B cells.
gp39 is expressed on anti-CD3-activated Th, and binds CD40 on the B cell, driving B cell cycle entry. In this study, the signal-transduction pathway initiated in B cells as a consequence of interacting with activated Th is examined. Unlike anti-membrane Ig (anti-mlg) or anti-MHC class II, plasma membranes (PM) isolated from anti-CD3-activated Th, PMAct did not trigger an increase in the B cell intracellular concentrations of cAMP or calcium. In addition, PMAct did not stimulate protein kinase C activation as measured by myristoylated alanine-rich C-kinase substrate (MARCKS) phosphorylation and protein kinase C translocation. The failure to detect these biochemical events may be caused by the asynchrony with which PMAct induce these normally transient biochemical changes. Alternatively, PMAct may not trigger these events. PMAct did induce the tyrosine phosphorylation of several B cell substrates. Neutralizing Abs directed against gp39 inhibited PMAct-induced protein tyrosine phosphorylation of B cell substrates. These results suggest that cognate interactions in B cells initiate a signal-transduction pathway that is different from the pathway initiated by cross-linking of mlg or MHC class II.
Marshall
L S
LS
Biochemistry Graduate Program, Dartmouth Medical School, Lebanon, NH 03756.
Shepherd
D M
DM
Ledbetter
J A
JA
Aruffo
A
A
Noelle
R J
RJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D051379:Mice; D008811:Mice, Inbred DBA; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; C000619711:Marcks protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D014443:Tyrosine; D012313:RNA; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium