Relative position and strengths of poly(A) sites as well as transcription termination are critical to membrane versus secreted mu-chain expression during B-cell development.

Abstract

During B-cell differentiation, there is a dramatic switch in the RNA products of the immunoglobulin mu heavy chain transcription unit. In the mature B cell there is roughly equal production of the microseconds and the micron RNA, whereas in the antibody-secreting plasma cell there is nearly exclusive production of the microseconds RNA. A plasmid containing the entire mu transcription unit was properly regulated when assayed by transient transfection in a B lymphoma and a plasmacytoma. In contrast, no such regulation was observed with separate plasmids that could produce only one or the other RNA. Instead, the micron poly(A) site was utilized more efficiently than the microseconds poly(A) site, irrespective of the cell type. We also found that transcription termination prior to the micron poly(A) site in plasmacytomas contributes to preferential production of microseconds RNA in these cells. Finally, reducing the distance between the two poly(A) sites improved the use of the micron site at the expense of the use of the microseconds in B lymphoma cells, suggesting a competition for a limiting factor. Such competition was not apparent in plasmacytomas. We conclude that relative poly(A) site strength and the position of the poly(A) sites within the transcription unit, coupled with a changing concentration of a limiting factor, as well as transcription termination prior to the micron poly(A) site, all play a role in determining the expression of the mu locus during B-cell development.