The relative abundance of membrane and secreted immunoglobulin

Analysis of nuclear RNA has shown that the precursors of the membrane and secreted forms in the nucleus are present in the same ratio as the mRNAs in the cytoplasm [126]. This demonstrates that the relative production of fim and jus mRNAs is determined in the nucleus, although, as described in Section 4.4., the overall ratio of membrane IgM to secreted IgM produced is also controlled at the translational and/or posttranslational levels. 

There is evidence which supports the proposal that it may be possible to polyadenylate the primary IgH transcript at a membrane polyadenylation site and then subsequently cleave and polyadenylate at a secreted site. A small RNA has been described that is polyadenylated at the am polyadenylation site and that appears to have a 5 terminus close to the as site [127]. Similarly, an RNA has also been described which is polyadenylated at /j.m and contains the CmM exons but not the other exons of the /u. gene [156]. However, these RNAs have either been described in B lymphomas or in a T cell lymphoma/plasmacytoma hybrid but they have not been found - as one might more reasonably expect - in several immunoglobulin-secreting plasmacytomas analysed [127,155,156]. Therefore, the significance of sequential cleavage/polyadenylation in the generation of mRNA for the secreted form of IgH polypeptides remains unclear. 

In conclusion, the relative production of fim and jus is controlled at the level of RNA processing in the nucleus. An attractive model for the regulation of /xm//us production involves competition between cleavage/polyadenylation at the /xs site and splicing of the (3 4 and CmM1 exons. 

73 Mizushina-Sugano. J. and Roeder, R.G. (1986) Proc. Natl. Acad. Sci. USA 83, 8511-8515. 

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