Defective calcium-dependent signal transduction in B lymphocytes of a certain common variable immunodeficiency.
Two different common variable immunodeficiency patients were studied. Patient 1 showed hypogammaglobulinemia in all major classes of gammaglobulins and slightly reduced percentages of circulating CD19+ cells, CD20+ cells and surface IgG-or IgA-bearing cells with a normal percentage of surface IgM-bearing cells. Patient 2 showed normal levels in IgM with IgG and IgA deficiencies and almost normal percentages of circulating CD19+ cells, CD20+ cells and surface IgM-, IgG- or IgA-bearing cells. The proliferative responses of peripheral blood mononuclear cells to B cell mitogen, Staphylococcus aureus Cowan I, were reduced in patient 1 but not in patient 2. The intracellular calcium concentrations in lymphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus from patient 2 were increased after anti-mu stimulation. The concentrations were scarcely increased in LCLs from patient 1. These results suggest that B cells of patient 1 have a defective Ca(2+)-dependent signal transduction pathway, resulting in a failure of cell activation and cell proliferation. The defect in B cells of patient 2 may exist on immunoglobulin gene switching or expression rather than the Ca(2+)-dependent signal transduction pathway.
Kondo
N
N
Department of Pediatrics, Gifu University School of Medicine, Japan.
Inoue
R
R
Yano
M
M
Hayashi
T
T
Miwa
Y
Y
Kasahara
K
K
Yamasaki
M
M
Utsumi
M
M
Shinbara
M
M
Orii
T
T
D000361:Agammaglobulinemia / Q000209:etiology; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002472:Cell Transformation, Viral; D002648:Child; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D004247:DNA / Q000096:biosynthesis; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D015398:Signal Transduction / Q000187:drug effects*
D015703:Antigens, CD; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D004247:DNA; D002118:Calcium