| Autor: |
Lu, Kristina T., Dryer, Rebecca L., Song, Charles, Covey, Lori R. |
| Zdroj: |
Journal of Leukocyte Biology; September 2005, Vol. 78 Issue: 3 p620-629, 10p |
| Abstrakt: |
Our previous investigation of a patient (pt1) with non‐X‐linked hyper‐immunoglobulin M syndrome revealed a CD40‐mediated defect in B cell activation that resulted in low CD23 expression and absence of germ‐line transcription and class‐switch recombination. These deficiencies were complemented in vitro by a high threshold of sustained sinaling through CD40. To further analyze the signaling defect in pt1 B cells, two types of Epstein‐Barr virus lymphoblastoid cell lines (LCLs) were generated that either constitutively expressed the viral transforming protein latent membrane protein‐1 (LMP1; pt1‐LCL) or expressed it under the control of a tet‐inducible promoter (pt1‐LCLtet). Because LMP1 signals through the CD40 pathway, the pt1‐LCL and pt1‐LCLtetlines allow comparison of downstream functions in response to either constitutive LMP1 signals or regulated LMP1 and CD40 signals. Immortalized pt1‐LCLs were initially CD23lo/CD38hiand reverted to a CD23hi/CD38lophenotype upon extended growth in culture, suggesting that the CD40 defect was reversed by selection and/or constitutive expression of LMP1. In contrast, pt1‐LCLtetcells retained the CD23lo/CD38hiphenotype after extended periods of culture and failed to up‐regulate CD23 in response to CD40 signals. Analysis of pt1‐LCLtetcells in response to the CD40 signals in the presence or absence of LMP1 revealed that mitogenic activation resulted only from LMP1 and not CD40, indicating a difference in the response of pt1 B cells to these two distinct signals. Together, these data demonstrate that the pt1‐LCLtetcells maintain the CD40‐related defect and provide a unique approach to study the independent effects of LMP1‐ and CD40‐directed signals. |
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