Yuan D, Witte P L, Tan J, Hawley J, Dang T
Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
J Immunol. 1996 Sep 1;157(5):2073-81.
Early IgM+ B cells express little or no membrane IgD due to the low abundance of delta mRNA. Extensive transcriptional termination regulated by sequences in the intronic region between mu and delta heavy chain genes may be the primary reason for the lack of delta gene transcription. We have examined the effect of deletion of these sequences on the regulation of IgM and IgD heavy chain gene expression in transfectants as well as mice carrying this otherwise intact transgene. By run-on transcriptional measurement, we show that the delta exons are transcribed in bone marrow B cells from these transgenic mice. However, in spite of the induced premature synthesis of the full-length mu-delta transcript in pre-B cells, processing to delta mRNA does not occur until the lymphocytes express cell surface IgM. Therefore, during B cell development, synthesis of the full-length transcript is a necessary but not sufficient condition for initiation of delta mRNA synthesis. Furthermore, unexpectedly, the abrogation of transcriptional termination was found to also affect the processing of the primary transcript to microM mRNA. These results show that expression of IgD in primary B cells is stringently regulated and closely linked to IgM expression.
早期IgM⁺ B细胞由于δ mRNA丰度低而几乎不表达或不表达膜IgD。μ和δ重链基因之间内含子区域的序列调控的广泛转录终止可能是δ基因转录缺失的主要原因。我们研究了缺失这些序列对转染细胞以及携带该完整转基因的小鼠中IgM和IgD重链基因表达调控的影响。通过连续转录测量，我们发现这些转基因小鼠骨髓B细胞中的δ外显子被转录。然而，尽管在前B细胞中诱导了全长μ-δ转录本的过早合成，但直到淋巴细胞表达细胞表面IgM时才会加工成δ mRNA。因此，在B细胞发育过程中，全长转录本的合成是启动δ mRNA合成的必要但不充分条件。此外，出乎意料的是，发现转录终止的消除也会影响初级转录本加工成μ mRNA的过程。这些结果表明，原代B细胞中IgD的表达受到严格调控，并且与IgM表达密切相关。
