Regulation of Ig gene expression in normal lymphocytes. I. The half‐life of secreted μ chain mRNA differs from that of membrane μ chain mRNA in resting and activated B cells

Abstract

Resting and activated B lymphocytes were used to study the stability of mu-specific precursor and mature mRNA. Resting cells which predominantly process the mu precursor towards micron do so rather slowly as reflected in a precursor half-life (T1/2) of 1-2 h. The small amount of secreted mu chain mRNA is fairly stable (T1/2 approximately 8 h) compared to membrane mu chain (T1/2 approximately 4 h). After activation the precursor processing is very fast (T1/2 approximately 10 min) and the stability of mu2, which now predominates, increases (T1/2 approximately 16 h) while the half-life of micron remains at about 4 h. The data indicate that normal B cells regulate mu-specific mRNA stability differently from tumor cells of the B cell lineage.

Regulation of immunoglobulin gene expression in normal lymphocytes II. Mechanisms of down‐regulation of immunoglobulin secretion after engagement of the B cell antigen receptor

“…Fig. 5 shows that in LPS-activated cells, the precursor is preferentially processed towards ps rather than totally conserve the processing phenotype of resting cells [9] or, at least, reduce the efficiency of the alternative processing towards ps.…”

Inefficient processing of mRNA for the membraneform of IgE is a genetic mechanism to limit recruitment of IgE‐secreting cells

“…The choice depends normally on the developmental stage of the B cell [11][12][13][14][15]. In resting B cells the ratio is approximately 1 : 1 for the mu (l) HC, but this ratio shifts in favor of the secreted form in plasma cells, resulting in a ratio of approximately 1 : 100 for the membrane (ml) versus the secreted form (sl), respectively.…”

U1A Inhibits Cleavage at the Immunoglobulin M Heavy-Chain Secretory Poly(A) Site by Binding between the Two Downstream GU-Rich Regions

“…This results in the secretory form of mRNA which encodes the heavy chain of a secreted antibody. The secretory form of -mRNA is expressed in differentiated cells by a combination of increased cleavage at the secretory poly(A) site and increased stability of the secretory mRNA itself (1,3,10,12).3Ј end cleavage in metazoans takes place on the recognition of a bipartite poly(A) signal consisting of a consensus AAUAAA and a less-defined GU-rich sequence, upstream and downstream of the cleavage site, respectively, by components of the cleavage-polyadenylation complex. These consist of the multimeric cleavage polyadenylation specificity factor (CPSF) and cleavage stimulatory factor (CstF), of which the 64-kDa component (CstF64K) recognizes the GU-rich region, as well as cleavage factors I and II and poly(A) polymerase (reviewed in reference 31).…”

“…This results in the secretory form of mRNA which encodes the heavy chain of a secreted antibody. The secretory form of -mRNA is expressed in differentiated cells by a combination of increased cleavage at the secretory poly(A) site and increased stability of the secretory mRNA itself (1,3,10,12).…”