Increased transcription and coordinate stabilization of mRNAs for secreted immunoglobulin alpha heavy chain and kappa light chain following stimulation of immunoglobulin A expressing B cells.
Immunoglobulin A (IgA) plays a key role in host protection at mucosal surfaces, yet little is known regarding the molecular mechanisms that govern the expression of this isotype. The studies herein investigated mechanisms that control IgA secretion in response to stimulation with interleukin-4 and interleukin-5, cytokines which are known to regulate IgA responses, and to bacterial lipopolysaccharide. Two mechanisms were shown to govern agonist induced IgA expression in a murine IgA expressing B cell line. In the initial period after stimulation, increased mRNA levels for the secreted form of alpha heavy chain (alpha s), and kappa light chain were paralleled by a transient increase in transcription rates of the corresponding genes. However, with prolonged agonist stimulation, gene transcription rates decreased to near control levels, and increased mRNA levels were associated with a coordinate increase in alpha s and kappa mRNA stability. In striking contrast, these agonists did not affect levels or stability of mRNA for the membrane form of alpha heavy chain (alpha m). Alpha s mRNAs contained multiple poly(A) addition sites located 13-32 nucleotides downstream of a single AAUAAA sequence. Nonetheless, the differential usage of these sites as a mechanism for controlling alpha s mRNA stability could be excluded, since the relative abundance of these different alpha s mRNAs did not differ significantly after agonist stimulation. These data, taken together, suggest that sequences within 107 nucleotides of the 3' end of alpha s mRNA, which are absent in alpha M mRNA, are required for the regulation of alpha s mRNA stability, possibly by acting as targets for regulated trans-acting cellular factors.
Eckmann
L
L
Department of Medicine, University of California, San Diego, La Jolla 92093.
Huang
G T
GT
Smith
J R
JR
Morzycka-Wroblewska
E
E
Kagnoff
M F
MF
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D011061:Poly A / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D016207:Cytokines; D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011061:Poly A