BOB.1/OBF.1 deficiency affects marginal-zone B-cell compartment.
Marginal-zone (MZ) B cells represent a first line of defense against particulate blood-borne antigens. Together with the B1 cells, they are responsible for the early response against type II T-independent antigens. The molecular pathways controlling the development of MZ B cells are only poorly understood. We found that these cells are virtually absent in mice deficient in the BOB.1/OBF.1 coactivator. Loss of these B cells was demonstrated by the lack of cells showing the appropriate cell surface phenotype but also by histological analyses and tri-nitro-phenol-Ficoll capturing. The lack of these cells is a B-cell-intrinsic defect, as shown by bone marrow complementation experiments. We also show that the expression of BOB.1/OBF.1 in peripheral B cells is required for the development of MZ B lymphocytes. Our analysis of BOB.1/OBF.1-deficient splenic B cells reveals alterations in cell motility, tumor necrosis factor receptor expression, and B-cell receptor (BCR) signaling. These changes could contribute to the loss of MZ B lymphocytes by altering the maturation of the cells. Interestingly, development of and BCR signaling in B1 B cells are completely normal in BOB.1/OBF.1 mutant mice.
Samardzic
Tatjana
T
Department of Physiological Chemistry, Ulm University, 89081 Ulm, Germany.
Marinkovic
Dragan
D
Nielsen
Peter J
PJ
Nitschke
Lars
L
Wirth
Thomas
T
D000818:Animals; D000941:Antigens / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D019070:Cell Lineage; D002465:Cell Movement / Q000502:physiology; D002469:Cell Separation; D005362:Ficoll / Q000031:analogs & derivatives* / Q000378:metabolism; D005434:Flow Cytometry; D017930:Genes, Reporter; D006241:Haptens / Q000378:metabolism; D007114:Immunization; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014301:Trinitrobenzenes / Q000378:metabolism
D000941:Antigens; D053265:B-Cell Activation Factor Receptor; D006241:Haptens; D008565:Membrane Proteins; C490424:Pou2af1 protein, mouse; D018124:Receptors, Tumor Necrosis Factor; C020529:TNP-ficoll; C486662:Tnfrsf13c protein, mouse; D015534:Trans-Activators; D014301:Trinitrobenzenes; D005362:Ficoll; D002118:Calcium