Activation of NF-kappaB promotes the transition of large, CD43+ pre-B cells to small, CD43- pre-B cells.
The regulation of the transcription factor nuclear factor-kappaB (NF-kappaB) during B-cell development was examined using cells isolated from the bone marrow of transgenic mice expressing a kappaB luciferase reporter gene. The results indicate that the highest level of NF-kappaB activity is present in cells expressing the pre-B-cell receptor. Furthermore, cross-linking of Igbeta on CD43(+) pre-B cells is able to activate NF-kappaB in recombination-activating gene 1-deficient mice, preceding their further differentiation into CD43(-) pre-B cells. Expression of a dominant negative form of IkappaBalpha using a transgenic approach or by retroviral infection leads to a reduction in the number of CD43(+) pre-B cells. These data therefore indicate that activation of NF-kappaB in CD43(+) pre-B cells, as a result of signaling by the pre-B-cell receptor, facilitates the continued development of large, CD43(+) pre-B cells into small CD43(-) pre-B cells.
Jimi
Eijiro
E
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Phillips
Roderick J
RJ
Rincon
Mercedes
M
Voll
Reinhard
R
Karasuyama
Hajime
H
Flavell
Richard
R
Ghosh
Sankar
S
D000818:Animals; D000906:Antibodies; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens / Q000032:analysis; D008156:Luciferases; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D054420:Pre-B Cell Receptors; D020569:Proto-Oncogene Proteins c-rel / Q000032:analysis; D011947:Receptors, Antigen, B-Cell; D012190:Retroviridae / Q000235:genetics
D000906:Antibodies; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D054420:Pre-B Cell Receptors; D020569:Proto-Oncogene Proteins c-rel; D011947:Receptors, Antigen, B-Cell; D049452:Green Fluorescent Proteins; D008156:Luciferases; D017493:Leukocyte Common Antigens