IgG response is impaired in H2-c-<i>fos</i> transgenic mice

Takao, Shintaro; Sakai, Nobuo; Hatano, Masahiko; Hanioka, Keisuke; Rüther, Ulrich; Tokuhisa, Takeshi

doi:10.1093/intimm/3.4.369

Cited by 27 publications

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“…7C). However, IgG1-AFCs were not detected at all in the bone marrow of the H2-c-fos mice, repeating the Ig-class switch abnormality of H2-c-fos mice (16,17). These results suggest that c-Fos/AP-1 positively regulates terminal differentiation of Ag-activated B cells.…”

Section: C-fos Augments Terminal Differentiation Of Ag-specific B Celmentioning

confidence: 83%

“…We generated transgenic mice carrying the murine c-fos gene under the control of the murine MHC gene (H2-K b ) promoter (H2-c-fos) (15). Splenic T and B cells from the mice constitutively express a high level of the exogenous c-fos gene (16). When H2-c-fos mice are immunized with T-dependent Ags, the mice can make the reduced size of germinal centers and fail to generate memory B cells in the spleen (16,17).…”

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confidence: 99%

“…Splenic T and B cells from the mice constitutively express a high level of the exogenous c-fos gene (16). When H2-c-fos mice are immunized with T-dependent Ags, the mice can make the reduced size of germinal centers and fail to generate memory B cells in the spleen (16,17). These results suggest that the ectopic expression of c-Fos may accelerate commitment of germinal center B cells to a plasma cell fate.…”

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confidence: 99%

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A Role for c-fos/Activator Protein 1 in B Lymphocyte Terminal Differentiation

Ohkubo

Arima

Arguni

et al. 2005

The Journal of Immunology

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Expression of B lymphocyte-induced maturation protein 1 (Blimp-1) transcription factor is essential for promoting B cell differentiation into plasma cells. However, a critical transcription factor for Blimp-1 expression in activated B cells is unclear. When splenic B cells were stimulated with CD40 ligand (CD40L) and IL-4, terminal differentiation was induced in the B cells from c-fos transgenic (H2-c-fos) mice but barely in those from control littermates and from c-fos-deficient mice. AP-1 family and Blimp-1 mRNAs were transiently induced in the control B cells, and overexpression of c-Fos induced a sufficient amount of Blimp-1 for terminal differentiation in the H2-c-fos B cells. When normal and c-fos-deficient B cells were stimulated with LPS, a sufficient amount of Blimp-1 for terminal differentiation was induced in those B cells. However, expression of c-fos/AP-1 family mRNAs in LPS-stimulated normal B cells was similar to that of normal B cells stimulated with CD40L and IL-4. EMSA and chromatin immunoprecipitation assays using the AP-1-binding DNA sequence in the murine Blimp-1 promoter region demonstrated that AP-1-binding activity in nuclear protein of LPS-stimulated normal B cells was prolonged more than that in normal B cells stimulated with CD40L and IL-4. Furthermore, the percentage of CD138+ B cells within germinal center B cells in the spleen and the number of Ab-forming cells in the bone marrow of H2-c-fos mice was larger than that of control mice 12 days after immunization. Thus, although c-Fos is not essential for Blimp-1 expression, c-Fos/AP-1 positively regulates Blimp-1 expression and terminal differentiation of activated B cells.

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Section: C-fos Augments Terminal Differentiation Of Ag-specific B Celmentioning

confidence: 83%

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confidence: 99%

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confidence: 99%

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A Role for c-fos/Activator Protein 1 in B Lymphocyte Terminal Differentiation

Ohkubo

Arima

Arguni

et al. 2005

The Journal of Immunology

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“…In vivo experiments have demonstrated that overexpression of c-fos in transgenic and embryonic stem cell chimeric mice affects bone and cartilage cell lineages (7,22,27). With respect to hematopoietic cells, high levels of c-fos mRNA expression are found in macrophages, neutrophils, and T lymphocytes (6,16,20,21), and overexpression of c-fos in hematopoietic organs of transgenic mice results in an altered rate of T-cell maturation (23) and in impaired B-cell function (26). Furthermore, c-foslv-jun double-transgenic mice exhibit delayed development of early B cells and a low interleukin-7 (IL-7)-dependent proliferation capacity of bone marrow cells (5).…”

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confidence: 99%

Mice lacking c-fos have normal hematopoietic stem cells but exhibit altered B-cell differentiation due to an impaired bone marrow environment.

Okada¹,

Wang²,

Grigoriadis³

et al. 1994

Mol. Cell. Biol.

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Mice lacking c-fos develop severe osteopetrosis with deficiencies in bone remodeling and exhibit extramedullary hematopoiesis, thymic atrophy, and altered B-cell development. In this study, we have used these mice to characterize in detail the developmental potential of hematopoietic stem cells lacking c-fos and to analyze how the lymphoid differentiation is altered. In c-fos -/- mice, B-cell numbers are reduced in the spleen, lymph nodes, and the peripheral blood as a result of a marked reduction (> 90%) in the number of clonogenic B-cell precursors. In contrast, the number and lineage distribution of myeloid progenitor cells are not affected. The thymic defects observed in a large number of these mice correlate with their health status, suggesting that this may be an indirect effect of the c-fos mutation. In vitro differentiation and bone marrow reconstitution experiments demonstrated that hematopoietic stem cells lacking c-fos can give rise to all mature myeloid as well as lymphoid cells, suggesting that the observed B lymphopenia in the mutant mice is due to an altered environment. Transplantation of wild-type bone marrow cells into newborn mutant mice resulted in the establishment of a bone marrow space and subsequent correction of the B-cell defect. These results demonstrate that hematopoietic stem cells lacking Fos have full developmental potential and that the observed defect in B-cell development is most likely due to the impaired bone marrow environment as a consequence of osteopetrosis.

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“…Myc gene deregulation alone is not su cient to cause a fully transformed phenotype and requires the cooperative interactions of other gene(s) to induce a state of malignancy (Cleveland et al, 1986;Sinn et al, 1987;Cory and Adams, 1988;Harris et al, 1988;Kurie et al, 1990;Berns, 1991;Breuer et al, 1991;Takao et al, 1991). The ability of myc genes to participate in lymphomagenesis has been reported in transgenic mice that carry a deregulated c-myc gene (Adams et al, 1985;Leder et al, 1986;Suda et al, 1987;Schmidt et al, 1988;Alexander et al, 1989;Berns et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Transgenic N-myc mouse model for indolent B cell lymphoma: tumor characterization and analysis of genetic alterations in spontaneous and retrovirally accelerated tumors

et al. 1998

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Little is known about stepwise deregulation of speci®c genes leading to lymphoid malignancy. Aberrant myc gene expression in transgenic mice is correlated with B cell lymphomagenesis. We generated a unique transgenic mouse model in which deregulated murine Em-N-myc transgene expression leads to development of indolent B cell lymphoma. Tumor cells were monoclonal, morphologically mature and surface immunoglobulin expressing B cells. Tumors arose in a disease course and exhibited a cytoarchitectural appearance reminiscent of human follicular lymphoma. Yet tumor cells were staged as preB since they failed to rearrange the immunoglobulin light chain genes. Retroviral insertion mutagenesis analyses of adult transgenic mice infected as newborns with murine leukemia virus revealed decreased disease latency, increased lymphoma incidence and a histologically more mature tumor type. Proviral insertion sites were not equivalent when accelerated Em-N-myc indolent lymphomas were compared to accelerated c-myc preB cell lymphomas. The bcl-2 gene was not disrupted in either spontaneous or provirally accelerated Em-N-myc lymphomas. These ®ndings suggest that tumor progression in N-myc-associated indolent B cell lymphoma can proceed along diverse pathways involving distinctly di erent combinations of deregulated and/or intact genes than those pathways described in highly aggressive forms of myc-related murine preB cell disease.

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IgG response is impaired in H2-c-fos transgenic mice

Cited by 27 publications

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A Role for c-fos/Activator Protein 1 in B Lymphocyte Terminal Differentiation

A Role for c-fos/Activator Protein 1 in B Lymphocyte Terminal Differentiation

Mice lacking c-fos have normal hematopoietic stem cells but exhibit altered B-cell differentiation due to an impaired bone marrow environment.

Transgenic N-myc mouse model for indolent B cell lymphoma: tumor characterization and analysis of genetic alterations in spontaneous and retrovirally accelerated tumors

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