Simultaneous activation of Ig and Oct-2 synthesis and reduction of surface MHC class II expression by IL-6.
Terminal differentiation of B cells to plasma cells in vivo is characterized by secretion of Ig and extinction of MHC class II expression on the cell surface. We show that IL-6 signaling leads to marked increases in the synthesis and secretion of Ig in clonal human B cell lines and newly isolated polyclonal B lymphocytes in vitro. The IL-6-induced cells resemble plasma cells in ultrastructure and in reduced expression of surface MHC class II. Enhanced Ig synthesis is a result of coordinated transcriptional activation of Ig genes without promoter or isotype specificity, and differential accumulation of the mRNA encoding the secreted form of Ig heavy chain. It is saturable and subject to negative control when IL-6 stimulation is prolonged. Coordinate with temporal changes in Ig synthesis, the DNA-binding activity and the synthesis of the B cell-enriched transcription factor Oct-2 are regulated. Thus, differentiation of B cells with IL-6 in vitro recapitulates the hallmarks of terminal B differentiation in vivo; Oct-2 may have a role in this process.
Natkunam
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Y
Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029.
Zhang
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X
Liu
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Chen-Kiang
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S
D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins; D006681:HLA-D Antigens / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D050813:Octamer Transcription Factor-2; D014066:Palatine Tonsil / Q000166:cytology; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D006681:HLA-D Antigens; D015850:Interleukin-6; D050813:Octamer Transcription Factor-2; C058435:POU2F2 protein, human; D014157:Transcription Factors