Myelomas and lymphomas expressing the Ig gamma 2a H chain gene have similar transcription termination regions.

Abstract

During B cell differentiation, the membrane and secretion specific forms of the Ig gamma-H chains of mouse are differentially expressed as a function of the developmental stage of the cell. Representatives of less differentiated and memory B cells (lymphomas) that have undergone the class switch to gamma 2a or gamma 2b H chains produce nearly equal amounts of membrane specific (gamma m) vs secretory specific (gamma s) mRNA. Fully differentiated gamma 2a or gamma 2b plasma cells and their tumors, myelomas, switch to higher levels of gamma s mRNA production relative to gamma m. Selective use of either the gamma s poly(A) site or the downstream gamma m poly(A) site accompanied by specific splicing events could modulate production of these two forms of mature gamma H chain mRNA. Alternatively, transcription termination could be modulated. Through a combination of hybrid protection and in vitro nascent RNA analyses of transcripts from gamma H chain-producing cells arrested at various stages of development, we have mapped transcription termination in both lymphomas (gamma s approximately gamma m mRNA) and in myelomas (gamma s much greater than gamma m) mRNA. Regardless of the developmental stage of the cell, transcription proceeds at a significant level through both the secretory- and membrane-specific poly(A) sites and terminates at least 500 nucleotides downstream of the gamma m poly(A) site in both the gamma 2a and gamma 2b genes. We conclude that transcription termination does not play a major role in the switch to elevated levels of gamma s production in late stage gamma-producing myeloma cells and that alternative RNA processing alone must be responsible for the differential expression of the gamma H chain mRNA.