Cutting edge: impaired transitional B cell production and selection in the nonobese diabetic mouse.
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.
Quinn
William J
WJ
University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Noorchashm
Negin
N
Crowley
Jenni E
JE
Reed
Amy J
AJ
Noorchashm
Hooman
H
Naji
Ali
A
Cancro
Michael P
MP
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000473:pathology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002464:Cell Migration Inhibition; D002999:Clone Cells; D020022:Genetic Predisposition to Disease; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D013045:Species Specificity; D013234:Stem Cells / Q000166:cytology / Q000276:immunology