Formation of B-1 B cells from neonatal B-1 transitional cells exhibits NF-κB redundancy.
The stages of development leading up to the formation of mature B-1 cells have not been identified. As a result, there is no basis for understanding why various genetic defects, and those in the classical or alternative NF-κB pathways in particular, differentially affect the B-1 and B-2 B cell lineages. In this article, we demonstrate that B-1 B cells are generated from transitional cell intermediates that emerge in a distinct neonatal wave of development that is sustained for ~2 wk after birth and then declines as B-2 transitional cells predominate. We further show that, in contrast to the dependence of B-2 transitional cells on the alternative pathway, the survival of neonatal B-1 transitional cells and their maturation into B-1 B cells occurs as long as either alternative or classical NF-κB signaling is intact. On the basis of these results, we have generated a model of B-1 development that allows the defects in B-1 and B-2 cell production observed in various NF-κB-deficient strains of mice to be placed into a coherent cellular context.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Encarnacion
E
Montecino-Rodriguez
Kenneth
K
Dorshkind
D000818:Animals; D000831:Animals, Newborn; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D007150:Immunohistochemistry; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
D016328:NF-kappa B