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 is associated with both an increase in mu mRNA and the ratio of secreted to membrane forms of mu mRNA. In contrast, previous studies demonstrated that in vitro the secreted form of alpha mRNA (alpha s mRNA) predominates regardless of the stage of B cell differentiation. The present study demonstrates that alpha s mRNA predominates in both B cells derived from the germinal centers of murine Peyer's patches and in the functional IgA memory population, suggesting that in vitro events accurately represent the generation of a secretory IgA response in vivo. Although the predominant usage of the alpha s poly(A) site is due to RNA processing, it does not depend on either the alpha s poly(A) site, the 3' splice site associated with the exon encoding the membrane exon of IgA (alphaM) or the alphaM poly(A) sites. Analysis of the sequence of the intron between the alpha s terminus and alphaM (alpha s-alphaM intron) demonstrates the existence of several potential regulatory elements. Furthermore, the effects of deletions within the alpha s-alphaM intron on 3' terminus usage demonstrate that the predominant usage of the proximal terminus is not strictly dependent on the length of the intron. Together with previous work, these observations support the idea that choice of 3' terminus for all Ig heavy chain genes is regulated by a similar mechanism, but specific sequences within a heavy chain gene can impinge upon that mechanism.