Predominant usage of the proximal poly(A) site in alpha mRNAs is not intrinsic to the 3' termini

The maturation of IgM-expressing B cells to IgM-secreting plasma cells isassociated with both an increase in mu mRNA and the ratio of secreted tomembrane forms of mu mRNA. In contrast, previous studies demonstrated thatin vitro the secreted form of alpha mRNA (alpha s mRNA) predominatesregardless of the stage of B cell differentiation. The present studydemonstrates that alpha s mRNA predominates in both B cells derived fromthe germinal centers of murine Peyer's patches and in the functional IgAmemory population, suggesting that in vitro events accurately represent thegeneration of a secretory IgA response in vivo. Although the predominantusage of the alpha s poly(A) site is due to RNA processing, it does notdepend on either the alpha s poly(A) site, the 3' splice site associatedwith the exon encoding the membrane exon of IgA (alphaM) or the alphaMpoly(A) sites. Analysis of the sequence of the intron between the alpha sterminus and alphaM (alpha s- alphaM intron) demonstrates the existence ofseveral potential regulatory elements. Furthermore, the effects ofdeletions within the alpha s-alphaM intron on 3' terminus usage demonstratethat the predominant usage of the proximal terminus is not strictlydependent on the length of the intron. Together with previous work, theseobservations support the idea that choice of 3' terminus for all Ig heavychain genes is regulated by a similar mechanism, but specific sequenceswithin a heavy chain gene can impinge upon that mechanism.