Inhibition of human IgE production via Fc epsilon R-II stimulation results from a decrease in the mRNA for secreted but not membrane epsilon H chains.
We have previously shown, using IgE-anti-IgE immune complexes or mAb directed against CD23, that ongoing production of secreted IgE from the human plasma cell line AF-10 can be inhibited via the low affinity FcR for IgE (CD23). Changes occurring in the various forms of epsilon messenger RNA (epsilon mRNA) during this suppression were investigated. mRNA levels of lambda L chain were also assessed as well as beta-actin controls. Changes in membrane IgE and secreted IgE and lambda protein were simultaneously measured. Using a genomic probe corresponding to the human epsilon C region domains, three sets of epsilon-mRNA bands were identified (2.1, 3.0, and 3.8 kb). Only the largest of these (3.8 kb) contained the full epsilon membrane sequence and coded for true membrane epsilon protein. The 2.1-kb species of epsilon-mRNA contained no membrane sequence and coded for classical secreted epsilon protein. The intermediate epsilon-mRNA species (3.0 kb) was shown to contain membrane sequence but did not contain the full epsilon membrane sequence. The product of this mRNA would, in fact, function as a secreted protein. When IgE production by AF-10 cells was suppressed via Fc epsilon R-II, there was a 50% fall in the steady state levels of both forms of mRNA (2.1 and 3.0 kb) that code for secreted epsilon protein. Similarly, there was a fall in lambda-mRNA corresponding to the observed decrease in free lambda secretion. In marked contrast, levels of both membrane IgE protein and mRNA coding for membrane epsilon were unaltered on the suppressed AF-10 cells. These data suggest that inhibition of IgE production via Fc epsilon R-II is related to a fall in mRNA for secreted proteins (epsilon and lambda) and probably reflects a post-transcriptional mechanism effecting mRNA for secreted vs membrane protein mRNA.
Saxon
A
A
Hart and Louise Lyon Laboratory, Department of Medicine, UCLA School of Medicine 90024.
Kurbe-Leamer
M
M
Behle
K
K
Max
E E
EE
Zhang
K
K
D000936:Antigen-Antibody Complex / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D015152:Blotting, Northern; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D011961:Receptors, Fc / Q000502:physiology*; D017455:Receptors, IgE; D014407:Tumor Cells, Cultured
D000936:Antigen-Antibody Complex; D000944:Antigens, Differentiation, B-Lymphocyte; D007143:Immunoglobulin Heavy Chains; D007146:Immunoglobulin lambda-Chains; D008565:Membrane Proteins; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D017455:Receptors, IgE; D007073:Immunoglobulin E