The B lymphocyte-specific coactivator BOB.1/OBF.1 is required at multiple stages of B-cell development.
The transcriptional coactivator BOB.1/OBF.1 confers B-cell specificity on the transcription factors Oct1 and Oct2 at octamer site-containing promoters. A hallmark of the BOB.1/OBF.1 mutation in the mouse is the absence of germinal center development in secondary lymphoid organs, demonstrating the requirement for BOB.1/OBF.1 in antigen-dependent stages of B-cell differentiation. Here we analyzed earlier stages of B lymphopoiesis in BOB.1/OBF.1-deficient mice. Examination of B-cell development in the bone marrow revealed that the numbers of transitional immature (B220(+) IgM(hi)) B cells were reduced and that B-cell apoptosis was increased. When in competition with wild-type cells, BOB.1/OBF.1(-/-) bone marrow cells exhibited defects in repopulating the bone marrow B-cell compartment and were unable to establish a presence in the periphery of host mice. The defective bone marrow populations in BOB.1/OBF.1(-/-) mice were rescued by conditional expression of a BOB.1/OBF.1 transgene controlled by the tetracycline gene expression system. However, the restored populations did not restore the numbers of IgD(hi) B cells in the periphery, where the BOB.1/OBF.1 transgene was not expressed. These results show that BOB.1/OBF.1(-/-) B cells exhibit multistage defects in B-cell development, including impaired production of transitional B cells and defective maturation of recirculating B cells.
Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), Universität Würzburg, D-97078 Würzburg, Germany.
J
J
Hess
P J
PJ
Nielsen
K D
KD
Fischer
H
H
Bujard
T
T
Wirth
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism*; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D002469:Cell Separation; D004318:Doxycycline / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005838:Genotype; D007075:Immunoglobulin M / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D011401:Promoter Regions, Genetic; D013154:Spleen / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D019076:Transgenes
D000900:Anti-Bacterial Agents; D007075:Immunoglobulin M; C490424:Pou2af1 protein, mouse; D015534:Trans-Activators; D008156:Luciferases; D001973:Bromodeoxyuridine; D004318:Doxycycline