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The Ig kappa 3'-enhancer triggers gene expression in early B lymphocytes but its activity is enhanced on B cell
K B Meyer1, Y M Teh, M S Neuberger
1Wellcome/CRC Institute of Developmental Biology and Cancer, Cambridge, UK.
Ig kappa gene expression is controlled by two enhancers, one located within the major intron (Ei) and the other located downstream of C kappa (E3'). Whereas loss of E3' has previously been shown to diminish kappa expression, we show here that a rearranged kappa transgene lacking Ei is well expressed, even at the pre-B cell stage. This suggests that E3' alone might be sufficient to give properly regulated transcription throughout B cell development. Indeed, we show that a transgene composed of a beta-globin reporter linked to E3' is expressed in a B cell-specific manner, becoming activated at the late pro-B to pre-B cell stage but with dramatically enhanced activity on B cell activation. Thus, E3' becomes active as a transcription enhancer at the stage when V kappa-J kappa rearrangement is being initiated and is sufficient to yield an expression pattern in a linked reporter gene similar to that of fully rearranged kappa genes.
Ig kappa gene expression is controlled by two enhancers, one located within the major intron (Ei) and the other located downstream of C kappa (E3'). Whereas loss of E3' has previously been shown to diminish kappa expression, we show here that a rearranged kappa transgene lacking Ei is well expressed, even at the pre-B cell stage. This suggests that E3' alone might be sufficient to give properly regulated transcription throughout B cell development. Indeed, we show that a transgene composed of a beta-globin reporter linked to E3' is expressed in a B cell-specific manner, becoming activated at the late pro-B to pre-B cell stage but with dramatically enhanced activity on B cell activation. Thus, E3' becomes active as a transcription enhancer at the stage when V kappa-J kappa rearrangement is being initiated and is sufficient to yield an expression pattern in a linked reporter gene similar to that of fully rearranged kappa genes.