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Birth pangs: the stressful origins of lymphocytes
Shiv Pillai
Shiv Pillai
Published February 1, 2005
Citation Information: J Clin Invest. 2005;115(2):224-227. https://doi.org/10.1172/JCI24238.
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Commentary

Birth pangs: the stressful origins of lymphocytes

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Abstract

Inositol-requiring enzyme 1 (IRE1) is a transmembrane protein that signals from the ER and contributes to the generation of an active spliced form of the transcriptional regulator X-box–binding protein 1 (XBP1). XBP1 is required for the terminal differentiation of B lymphocytes into plasma cells, and IRE1 also participates in this differentiation event. A study in this issue of the JCI reveals, quite unexpectedly, that IRE1 is also required early in B lymphocyte development for the induction of the machinery that mediates Ig gene rearrangement.

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Shiv Pillai

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Figure 2

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A simplified overview of B cell development. Differentiation is initiate...
A simplified overview of B cell development. Differentiation is initiated in the bone marrow in an antigen-independent manner and is completed in the periphery in response to antigenic challenge. Rearrangement of the Ig heavy chain is initiated in pro–B cells and involves sequential DH to JH and VH to DJH rearrangements. Once light chain rearrangement is completed, B cells emigrate to the periphery and give rise to multiple peripheral lineages (not shown). Peripheral B cells activated by either T cell–dependent or T cell–independent antigens differentiate into plasma cells. In this issue, Zhang et al. (15) demonstrate that IRE1 is required for V(D)J recombination early in B cell development, but in a kinase- and endoribonuclease-independent fashion. IRE1 kinase and endoribonuclease activities are required for the splicing of XBP1 and plasma cell development. Pre-BCR, pre–B cell receptor.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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