Inefficient processing of mRNA for the membrane form of IgE is a genetic mechanism to limit recruitment of IgE-secreting cells.
Immunoglobulin E (IgE) is the key effector element in allergic diseases ranging from innocuous hay fever to life-threatening anaphylactic shock. Compared to other Ig classes, IgE serum levels are very low. In its membrane-bound form (mIgE), IgE behaves as a classical antigen receptor on B lymphocytes. Expression of mIgE is essential for subsequent recruitment of IgE-secreting cells. We show that in activated, mIgE-bearing B cells, mRNA for the membrane forms of both murine and human epsilon (epsilon) heavy chains (HC) are poorly expressed compared to mRNA for the secreted forms. In contrast, in mIgG-bearing B cells, mRNA for the membrane forms of murine gamma-1 (gamma1) and the corresponding human gamma4 HC are expressed at a much higher level than mRNA for the respective secreted forms. We show that these findings correlate with the presence of deviant polyadenylation signal hexamers in the 3' untranslated region (UTR) of both murine and human epsilon genes, causing inefficient processing of primary transcripts and thus poor expression of the proteins and poor recruitment of IgE-producing cells in the immune response. Thus, we have identified a genetic steering mechanism in the regulation of IgE synthesis that represents a further means to restrain potentially dangerous, high serum IgE levels.
Karnowski
Alexander
A
Metschnikoff Laboratory, Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Achatz-Straussberger
Gertrude
G
Klockenbusch
Cordula
C
Achatz
Gernot
G
Lamers
Marinus C
MC
D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012323:RNA Processing, Post-Transcriptional / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism*; D017455:Receptors, IgE / Q000172:deficiency / Q000235:genetics
D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E