Cell-autonomous role for NF-kappa B in immature bone marrow B cells.
The NF-kappaB transcription factors have many essential functions in B cells, such as during differentiation and proliferation of Ag-challenged mature B cells, but also during final maturation of developing B cells in the spleen. Among the various specific functions NF-kappaB factors carry out in these biologic contexts, their ability to assure the survival of mature and maturing B cells in the periphery stands out. Less clear is what if any roles NF-kappaB factors play during earlier stages of B cell development in the bone marrow. Using mice deficient in both NF-kappaB1 and NF-kappaB2, which are thus partially compromised in both the classical and alternative activation pathways, we demonstrate a B cell-autonomous contribution of NF-kappaB to the survival of immature B cells in the bone marrow. NF-kappaB1 and NF-kappaB2 also play a role during the earlier transition from proB to late preB cells; however, in this context these factors do not act in a B cell-autonomous fashion. Although NF-kappaB1 and NF-kappaB2 are not absolutely required for survival and progression of immature B cells in the bone marrow, they nevertheless make a significant contribution that marks the beginning of the profound cell-autonomous control these factors exert during all subsequent stages of B cell development. Therefore, the lifelong dependency of B cells on NF-kappaB-mediated survival functions is set in motion at the time of first expression of a full BCR.
Claudio
Estefania
E
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Saret
Sun
S
Wang
Hongshan
H
Siebenlist
Ulrich
U
D000818:Animals; D053265:B-Cell Activation Factor Receptor / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D052003:NF-kappa B p52 Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D053265:B-Cell Activation Factor Receptor; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; C073701:Nfkb1 protein, mouse