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The Journal of Immunology, 2006, 176: 7159-7164.
Copyright © 2006 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: Impaired Transitional B Cell Production and Selection in the Nonobese Diabetic Mouse1

William J. Quinn, III2, Negin Noorchashm2, Jenni E. Crowley, Amy J. Reed, Hooman Noorchashm, Ali Naji3 and Michael P. Cancro3,4

University of Pennsylvania School of Medicine, Philadelphia, PA 19104

Developing B cells undergo selection at multiple checkpoints to eliminate autoreactive clones. We analyzed B cell kinetics in the NOD mouse to establish whether these checkpoints are intact. Our results show that although bone marrow production is normal in NOD mice, transitional (TR) B cell production collapses at 3 wk of age, reflecting a lack of successful immature B cell migration to the periphery. This yields delayed establishment of the follicular pool and a lack of selection at the TR checkpoint, such that virtually all immature B cells that exit the bone marrow mature without further selection. These findings suggest that compromised TR B cell generation in NOD mice yields relaxed TR selection, affording autoreactive specificities access to mature pools.




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