Molecular crossroads

Plasma cells differentiate from B cells to secrete large amounts of immunoglobulin proteins. Maintaining an efficient plasma cell protein output is partially controlled by the unfolded protein response (UPR). Although the role of the UPR in cells undergoing stress is now beginning to be understood, the function of the UPR in B cell differentiation has been unclear. In the March 3 AOP Nature Immunology, Neal N. Iwakoshi and colleagues at the Harvard School of Public Health, Boston, Massachusetts, US, show that signals upstream and downstream of transcription factor X-box binding protein 1 (XBP-1) integrate plasma cell differentiation with the UPR (Nature Immunology, DOI:10.1038/ni907, March 3, 2003).

Iwakoshi et al. used B cells derived from XBP-1–/– mice and observed that UPR-induced splicing of XBP-1 was required to restore production of immunoglobulin. Interleukin-4 controlled the transcription of XBP-1, but XBP-1 post-transcriptional processing was dependent on synthesis of immunoglobulins during B cell differentiation. ...