التفاصيل البيبلوغرافية
| العنوان: |
Rapid B Cell Receptor-induced Unfolded Protein Response in Nonsecretory B Cells Correlates with Pro- Versus Antiapoptotic Cell Fate. |
| المؤلفون: |
Skalet, Alison H.1, Isler, Jennifer A.2, King, Leslie B.1, Harding, Heather P.3, Ron, David3, Monroe, John G.1 monroej@mail.med.upenn.edu |
| المصدر: |
Journal of Biological Chemistry. 12/2/2005, Vol. 280 Issue 48, p39762-39771. 10p. 7 Graphs. |
| مصطلحات موضوعية: |
*B cells, *ANTIGEN presenting cells, *ENDOTOXINS, *PLASMA cells, *ENDOPLASMIC reticulum, *CELL receptors, *MESSENGER RNA, *BIOLOGY |
| مستخلص: |
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 reported to anticipate endoplasmic reticulum stress prior to immunoglobulin production. Here we demonstrate that activation of a physiologic UPR is not limited to cells undergoing secretory cell differentiation. We 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 induces activation, since a UPR is also induced in transitional immature B cells that respond to BCR stimulation with a rapid apoptotic fate. This response involves sustained up-regulation of Chop mRNA indicative of a terminal UPR. Whereas 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. These studies establish a system whereby a terminal or adaptive UPR can be alternatively triggered by physiologic stimuli. [ABSTRACT FROM AUTHOR] |
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