Secretion and cell surface expression of IgG1 are impaired in human B lymphoblasts that lack HLA-A, -B, and -C antigens.
B-lymphoblastoid cell line (LCL) 721.221 lacks HLA-A, -B, and -C class I antigens and transcripts as a result of gamma-ray-induced mutations. LCL 721, from which mutant .221 was derived, produces membrane and secreted forms of IgG1(kappa). In contrast, IgG expression in .221 had these characteristics: (i) gamma 1 heavy chains were diminished by 98% but were detectable with chain-specific antibodies in cell lysates; (ii) kappa light chains were present at normal levels in cell lysates and free kappa chains were secreted; (iii) cell-surface-associated IgG and secreted IgG were absent. Mutants that had partially reduced amounts of class I antigens continued to secrete IgG; however, both the absolute amount of IgG secreted and the relative amount of kappa vs. intact IgG secreted were abnormal in such partially class I-deficient cells. The failure to export IgG and the deficiency of HLA-A, -B, and -C were not merely coincidental in mutant .221, since production of IgG was restored by transferring a functional HLA-A, -B, or -C gene into .221. Cell surface antigen expression of cloned HLA-A, -B, and -C transgenes introduced into .221 was comparable to that of the same genes in their normal chromosomal locations. These observations reveal a relation between production of HLA class I gene products and production of IgG.
Burlingham
W J
WJ
Department of Surgery, University of Wisconsin-Madison 53792.
Ceman
S S
SS
DeMars
R
R
D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis* / Q000235:genetics
D000911:Antibodies, Monoclonal; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell