Telomerase activity is induced in human peripheral B lymphocytes by the stimulation to antigen receptor.
To understand the molecular events for the proliferation of B cells, we studied the induction of telomerase activity in vitro after stimulation to B-cell antigen receptor (BCR) on human peripheral B cells. Although unstimulated purified B cells of tonsils and peripheral blood from healthy volunteers do not express detectable telomerase activity, anti-IgM beads induce telomerase activity in these B cells. Soluble anti-IgM antibody (Ab) alone does not induce telomerase activity, but the second signal, given by either one of the cytokines of interleukin-2 (IL-2), IL-4, and IL-13 or by anti-CD40 monoclonal Ab (MoAb), is effective as the costimulation for the induction of the activity. Stimulation with anti-IgM Ab and anti-CD40 MoAb induces telomerase activity in most mature B cells of the tonsils and peripheral blood. The stimuli to both IgM and IgD receptors similarly induce the activity. Induction of telomerase activity is accompanied with the proliferation of B cells, but is not absolutely correlated with the extent of B-cell growth. Phorbol dibutylate (PDB) plus calcium (Ca) ionophore (PDB/Ca), which replace the activation through BCR and the costimulatory molecules, also induce telomerase activity. Moreover, it is suggested that phosphoinositide (PI) 3-kinase plays a role for the induction of telomerase activity in B cells stimulated with anti-IgM Ab and anti-CD40 MoAb. These results suggest that telomerase activity is induced in the B-cell activation of the antigen specific immune response.
Igarashi
H
H
Department of Immunology, Kumamoto University School of Medicine, Japan.
Sakaguchi
N
N
D000730:Androstadienes / Q000494:pharmacology; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007476:Ionophores / Q000494:pharmacology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000502:physiology; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051562:Proto-Oncogene Proteins c-bcr; D011947:Receptors, Antigen, B-Cell / Q000187:drug effects / Q000276:immunology*; D015398:Signal Transduction; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D000077191:Wortmannin
D000730:Androstadienes; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016207:Cytokines; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007476:Ionophores; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; C039951:anti-IgD; C044203:anti-IgM; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr; D019098:Telomerase; D002118:Calcium; D000077191:Wortmannin