Abstract
The differentiation of B cells into immunoglobulin-secreting plasma cells is controlled by two transcription factors, Blimp-1 and XBP1. By gene expression profiling, we defined a set of genes whose induction during mouse plasmacytic differentiation is dependent on Blimp-1 and/or XBP1. Blimp-1-deficient B cells failed to upregulate most plasma cell-specific genes, including xbp1. Differentiating xbp1-deficient B cells induced Blimp-1 normally but failed to upregulate genes encoding many secretory pathway components. Conversely, ectopic expression of XBP1 induced a wide spectrum of secretory pathway genes and physically expanded the endoplasmic reticulum. In addition, XBP1 increased cell size, lysosome content, mitochondrial mass and function, ribosome numbers, and total protein synthesis. Thus, XBP1 coordinates diverse changes in cellular structure and function resulting in the characteristic phenotype of professional secretory cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 81-93 |
| Number of pages | 13 |
| Journal | Immunity |
| Volume | 21 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 2004 |
| Externally published | Yes |
Bibliographical note
Funding Information:We would like to thank the members of all contributing labs for helpful discussions and generosity with reagents. We would like to thank all those who have thusfar contributed RNA samples and cDNA clones to the Mouse Lymphochip project (especially H. Morse, M. Potter, S. Janz, Y. Tagaya); Drs. E. Snapp and J. Lippincott-Schwartz for the gift of the ER-targeted gfp vector; and Bob Strausberg and the Cancer Genome Anatomy Project (National Cancer Institute) as well as the Leukemia and Lymphoma Society for funding, in part, the creation of the Mouse Lymphochip Microarray. This work was in part supported by NIH grants AI32412 (LHG), AI50659 (KC) and AI43576 (KC), an Award from the Multiple Myeloma Research Foundation (L.H.G.), and an Irvington Institute Postdoctoral Fellowship Award (N.N.I.).
