B lymphocytes from individuals with common variable immunodeficiency respond to B lymphocyte stimulator (BLyS protein) in vitro.
B lymphocyte stimulator (BLyS protein) is a member of the human TNF family of ligands. BLyS induces B-lymphocyte proliferation and Ig secretion in vitro and in vivo. These qualities suggest that it may be useful as a therapeutic in the treatment of immunodeficiencies characterized by low or absent serum immunoglobulin, such as common variable immunodeficiency (CVID). CVID is characterized by the inability to generate adequate serum Ig despite normal or slightly depressed peripheral B, T, and myeloid cell populations. We tested the ability of BLyS to stimulate B lymphocytes obtained from CVID patients. Among five patients studied, 60% (three of five) produced normal quantities of IgM when cultured in the presence of BLyS. B-cell proliferation among patients was comparable, with 60% (three of five) responding to BLyS stimulation. These results suggest that BLyS induces proliferative and Ig-secretory responses in B lymphocytes isolated from some CVID patients and lend support to its potential use in therapy of this disorder.
Metabolism Branch, NCI, NIH, 10 Center Drive MSC 1374, Bethesda, MD 20892, USA. dstew@helix.nih.gov
Donn M
DM
Stewart
Michael J
MJ
McAvoy
David M
DM
Hilbert
David L
DL
Nelson
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016367:Baculoviridae / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000276:immunology* / Q000628:therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; C120197:BLyS receptor; D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha