Alternative processing of IgA pre-mRNA responds like IgM to alterations in the efficiency of the competing splice and cleavage-polyadenylation reactions

Both the membrane-associated and -secreted Ig proteins are encoded by a single gene whose primary transcript is alternatively processed at its 3′ end. The relative use of the alternative processing pathways is regulated during B cell maturation. This alternative RNA processing involves two competing reactions, splicing from the last constant region exon to the membrane exon(s) and cleavage-polyadenylation at the secretory-specific poly(A) site. Studies with the IgM-encoding μ gene have shown that cell-specific regulation requires that the efficiencies of these two reactions be balanced; any gene modifications that substantially improve or reduce the efficiency of either reaction also abrogate the regulatory shift in alternative processing pathways. All of the Ig isotypes that undergo a membrane-to-secreted switch during B cell maturation have a similar gene structure, thus suggesting that they might all be regulated by the same mechanism. We show that RNA processing of chimeric μα genes containing modifications in the Cα3 exon size and the Cα3-αm intron size respond to these modifications as predicted by previous μ gene studies. In addition, RNA expression ratios from the chimeric μα genes are regulated in B cells and plasma cells. This provides good evidence that splicing and cleavage-polyadenylation in the α gene are balanced reactions that are regulated in the same way as in the μ gene.