Different patterns of calcium signaling triggered through two components of the B lymphocyte antigen receptor.
The engagement of the B cell antigen receptor is the first step of antigenic stimulation of B lymphocytes. This step is followed by a series of biochemical events, including the activation of protein-tyrosine kinases, phosphoinositide turnover, and multiple patterns of calcium mobilization, which lead to the regulation of gene transcription and cellular responses. The B cell antigen receptor complex is composed of membrane immunoglobulins (as antigen recognition subunits) and associated chains (Ig-alpha and Ig-beta) that couple the receptor to cytoplasmic protein kinases. To investigate independently the relative signaling capacity of Ig-alpha and Ig-beta, chimeric proteins containing their cytoplasmic domains were expressed in a B cell line. We found that Ig-alpha and Ig-beta activate two distinct intracellular signaling pathways. The engagement of Ig-alpha chimeras induces a complete release of calcium from intracellular stores, followed by transmembrane calcium influx and late cell activation signals, detected by lymphokine secretion. In contrast, Ig-beta chimeras do not induce lymphokine secretion or calcium influx, but induce short oscillatory release of calcium, dependent on the activity of the Ca-ATPase pump of the endoplasmic reticulum. These results provide a structural basis for the diversity of B cell responses.
Choquet
D
D
Unité 261, Institut National de la Santé et de la Recherche Médicale, Institut Pasteur, Paris, France.
Ku
G
G
Cassard
S
S
Malissen
B
B
Korn
H
H
Fridman
W H
WH
Bonnerot
C
C
D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002460:Cell Line; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D016393:Lymphoma, B-Cell; D046911:Macromolecular Substances; D008954:Models, Biological; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D019000:Phosphotyrosine; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014162:Transfection; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D015220:Calcium Channels; D007376:Interleukin-2; D046911:Macromolecular Substances; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D013729:Terpenes; D019000:Phosphotyrosine; D014443:Tyrosine; D019284:Thapsigargin; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; D002118:Calcium