رسالة جامعية
Characterization of an unexpected association between BCR-triggered non-secretory cell fate decisions and the unfolded protein response
| العنوان: | Characterization of an unexpected association between BCR-triggered non-secretory cell fate decisions and the unfolded protein response |
|---|---|
| المؤلفون: | Skalet, Alison H |
| المصدر: | 1 ; 163 ; AAI3165805 ; Dissertations available from ProQuest ; published |
| سنة النشر: | 2005 |
| المجموعة: | University of Pennsylvania: ScholaryCommons@Penn |
| مصطلحات موضوعية: | Immunology|Cellular biology |
| الوصف: | The adaptive unfolded protein response (UPR) is essential for the development of antibody-secreting plasma cells. B cells induced by lipopolysaccharide (LPS) to differentiate into plasma cells exhibit a nonclassical UPR that has been reported to anticipate endoplasmic reticulum stress prior to immunoglobulin production. Here I demonstrate that activation of a physiologic UPR is not limited to cells undergoing secretory cell differentiation. I identify B cell receptor (BCR) signaling as an unexpected physiologic UPR trigger and demonstrate that in mature B cells, BCR stimulation induces a short-lived UPR similar to the LPS-triggered nonclassical UPR. However, unlike LPS, BCR stimulation does not induce plasma cell differentiation. Furthermore, the BCR-induced UPR is not limited to cells in which BCR is an activating signal, as a UPR is also induced in transitional immature B cells, which respond to BCR stimulation with a rapid apoptotic fate. This response involves sustained upregulation of Chop mRNA indicative of a terminal UPR. While sustained Chop expression correlates with the ultimate fate of the BCR-triggered B cell and not its developmental stage, Chop−/− B cells undergo apoptosis, indicating that CHOP is not required for this process. The studies presented establish a system whereby a terminal or adaptive UPR can be alternatively triggered by physiologic stimuli. ; Ph.D. |
| نوع الوثيقة: | thesis |
| اللغة: | unknown |
| العلاقة: | https://upenn-prod.atmire.com/handle/20.500.14332/14967Test |
| الإتاحة: | https://doi.org/20.500.14332/14967Test https://upenn-prod.atmire.com/handle/20.500.14332/14967Test https://hdl.handle.net/20.500.14332/14967Test |
| رقم الانضمام: | edsbas.DBE23616 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |