XBP-1 specifically promotes IgM synthesis and secretion, but is dispensable for degradation of glycoproteins in primary B cells

Boaz Tirosh, Neal N. Iwakoshi, Laurie H. Glimcher, Hidde L. Ploegh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Differentiation of B cells into plasma cells requires X-box binding protein-1 (XBP-1). In the absence of XBP-1, B cells develop normally, but very little immunoglobulin is secreted. XBP-1 controls the expression of a large set of genes whose products participate in expansion of the endoplasmic reticulum (ER) and in protein trafficking. We define a new role for XBP-1 in exerting selective translational control over high and sustained levels of immunoglobulin M (IgM) synthesis. XBP-1-/- and XBP-1+/+ primary B cells synthesize IgM at comparable levels at the onset of stimulation with lipopolysaccharide or CpG. However, later there is a profound depression in synthesis of IgM in XBP-1-/- B cells, notwithstanding similar levels of μmRNA. In marked contrast, lack of XBP-1 does not affect synthesis and trafficking of other glycoproteins, or of immunoglobulin light chains. Contrary to expectation, degradation of proteins from the ER, using TCRα or US11-mediated degradation of class I major histocompatibility complex molecules as substrates, is normal in XBP-1-/- B cells. Furthermore, degradation of membrane μ was unaffected by enforced expression of XBP-1. We conclude that in primary B cells, the XBP-1 pathway promotes synthesis and secretion of IgM, but does not seem to be involved in the degradation of ER proteins, including that of μ chains themselves. JEM

Original languageAmerican English
Pages (from-to)505-516
Number of pages12
JournalJournal of Experimental Medicine
Volume202
Issue number4
DOIs
StatePublished - Aug 2005
Externally publishedYes

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