Developmental regulation of membrane and secretory Ig gamma 2b mRNA.

Abstract

To better understand the developmental regulation of membrane and secretory forms of Ig Heavy chain mRNA, mutations were made in a gamma 2b gene in vitro and assayed for their expression in cell lines representative of early and late stages of B cell development. Processing of the gamma 2b mRNA did not change with the amount of message produced, demonstrating that the production of predominantly secretory mRNA in plasma cells is not the consequence of increased message synthesis. The length of the intron between the secretory and membrane exons was found to affect the relative expression of secretory and membrane mRNA, but this effect was also observed in non-lymphoid cells, suggesting that the intron "gradient effect" does not identify the processing reaction which is regulated during B cell differentiation. Deletion of the signals for the splice from CH3 to the membrane exons resulted in the exclusive production of secretory mRNA irrespective of the developmental stage of the recipient cell, suggesting that this splice reaction plays a role in regulating these mRNA, and that competition between the two polyadenylation sites does not dictate the relative expression of the two forms of message. Appropriate ratios of the two forms were produced from a 2.3-kbp fragment of the gamma 2b gene containing the secretory cleavage and membrane splice signals in the context of a different transcription unit. These results suggest that the changes in the relative expression of secretory and membrane gamma 2b mRNA during B cell development are mediated by a competition between cleavage at the secretory polyadenylation and splicing from CH3 to the membrane exons.