Birth pangs: the stressful origins of lymphocytes
J. Clin. Invest. Shiv Pillai, et al. 115:224 doi:10.1172/JCI24238 [
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Figure 2A 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 D
H to J
H and V
H to DJ
H 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.