Failure of c-myc gene expression in B cells of some patients with common variable immunodeficiencies.
Many reports have shown that expression of the c-myc protooncogene represents an early event of lymphocyte activation. Calcium influx and activation of protein kinase C synergistically bypass the early signal transduction of lymphocyte activation. In this study, the c-myc message of B cells or B cell lines stimulated by 12-o-tetradecanoylphorbol-13-acetate (TPA), A23187, Staphylococcus aureus Cowan I (SAC), or anti-mu was not expressed or was poorly expressed in common variable immunodeficiency (CVID) patients whose B cells did not differentiate or only poorly differentiated to SAC plus recombinant interleukin 2, whereas the c-myc message of 1 CVID patient's B cells that differentiated well in IgM secretion to SAC plus recombinant interleukin 2 was well expressed when stimulated by TPA, A23187, SAC, or anti-mu. These results suggest that an abnormality exists in the early signal transduction process on some CVID patients' B cells and that it may be in the bypass by calcium influx and direct activation of protein kinase C.
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D015152:Blotting, Northern; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002648:Child; D017074:Common Variable Immunodeficiency / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D012313:RNA / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007070:Immunoglobulin A; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D000001:Calcimycin; D012313:RNA; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium