INCREASED TRANSCRIPTION AND COORDINATE STABILIZATION OF MESSENGER-RNAS 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 regulat e IgA responses, and to bacterial lipopolysaccharide, Two mechanisms w ere shown to govern agonist induced IgA expression in a murine IgA exp ressing B cell line, In the initial period after stimulation, increase d mRNA levels for the secreted form of alpha heavy chain (alpha(S)), a nd kappa light chain were paralleled by a transient increase in transc ription rates of the corresponding genes, However, with prolonged agon ist stimulation, gene transcription rates decreased to near control le vels, and increased mRNA levels were associated with a coordinate incr ease 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 multipl e poly(A) addition sites located 13-32 nucleotides downstream of a sin gle AAUAAA sequence, Nonetheless, the differential usage of these site s as a mechanism for controlling alpha(S) mRNA stability could be excl uded, since the relative abundance of these different alpha(S) mRNAs d id not differ significantly after agonist stimulation, These data, tak en together, suggest that sequences within 107 nucleotides of the 3' e nd of alpha(S) mRNA, which are absent in alpha(M) mRNA, are required f or the regulation of alpha(S) mRNA stability, possibly by acting as ta rgets for regulated trans-acting cellular factors.