Defective calcium response in B-chronic lymphocytic leukemia cells. Alteration of early protein tyrosine phosphorylation and of the mechanism responsible for cell calcium influx.
To study defective signal transduction via the Ag receptor of B-chronic lymphocytic leukemia cells (B-CLL), we examine in this report the Ca2+ response triggered by anti-mu antibody in 23 patients previously classified in three phenotypic groups. Altered Ca2+ changes are essentially found in CLL group II whose leukemic cells are characterized by a marked expression of the CD11b Ag. B-CLL cells from patients with a defective Ca2+ response present an altered pattern of protein tyrosine phosphorylation after anti-mu stimulation in comparison with normal human B cells and B-CLL cells from patients having a normal Ca2+ response. Most of the proteins usually tyrosine phosphorylated after the triggering of cell-surface IgM are concerned. This includes the gamma 1 isoform of phospholipase C, although the protein is normally present in B-CLL cells. These findings suggest that the interruption of the phosphoinositide pathway in B-CLL cells is very proximal, at the level in the signaling cascade between activated surface Ig receptors and protein tyrosine kinases. Simultaneously, we demonstrate that some low responding patients exhibit a decreased Ca2+ response to thapsigargin, an agent known to release intracellular Ca2+ without inositol 1,4,5-trisphosphate production. This suggests that an altered functioning of the mechanism leading to the cell Ca2+ influx in B cells can be also involved in the decreased Ca2+ response observed in B-CLL cells.
Michel
F
F
Laboratoire d'Immunologie Cellulaire et Tissulaire, CNRS UA 625, CH Pitié-Salpétrière, CERVI, Paris, France.
Merle-Béral
H
H
Legac
E
E
Michel
A
A
Debré
P
P
Bismuth
G
G
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D018845:CD11 Antigens; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology / Q000502:physiology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014443:Tyrosine / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D007075:Immunoglobulin M; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; D013729:Terpenes; C044203:anti-IgM; D014443:Tyrosine; D019284:Thapsigargin; D002118:Calcium