| First Author | Hu CC | Year | 2009 |
| Journal | EMBO J | Volume | 28 |
| Issue | 11 | Pages | 1624-36 |
| PubMed ID | 19407814 | Mgi Jnum | J:150026 |
| Mgi Id | MGI:3849551 | Doi | 10.1038/emboj.2009.117 |
| Citation | Hu CC, et al. (2009) XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells. EMBO J 28(11):1624-36 |
| abstractText | XBP-1, a transcription factor that drives the unfolded protein response (UPR), is activated in B cells when they differentiate to plasma cells. Here, we show that in the B cells, whose capacity to secrete IgM has been eliminated, XBP-1 is induced normally on induction of differentiation, suggesting that activation of XBP-1 in B cells is a differentiation-dependent event, but not the result of a UPR caused by the abundant synthesis of secreted IgM. Without XBP-1, B cells fail to signal effectively through the B-cell receptor. The signalling defects lead to aberrant expression of the plasma cell transcription factors IRF4 and Blimp-1, and altered levels of activation-induced cytidine deaminase and sphingosine-1-phosphate receptor. Using XBP-1-deficient/Blimp-1-GFP transgenic mice, we find that XBP-1-deficient B cells form antibody-secreting plasmablasts in response to initial immunization; however, these plasmablasts respond ineffectively to CXCL12. They fail to colonize the bone marrow and do not sustain antibody production. These findings define the role of XBP-1 in normal plasma cell development and have implications for management of B-cell malignancies. |
