Cutting edge: impaired transitional B cell production and selection in the nonobese diabetic mouse |
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Authors: | Quinn William J Noorchashm Negin Crowley Jenni E Reed Amy J Noorchashm Hooman Naji Ali Cancro Michael P |
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Institution: | University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. |
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Abstract: | 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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