Analysis of homozygous mutant chimeric mice: deletion of the immunoglobulin heavy-chain joining region blocks B-cell development and antibody production.

Jakobovits, Aya; Vergara, German J.; Kennedy, Jacqueline; Hales, Joanna F.; McGuinness, Ryan; Casentini-Borocz, Denise E.; Brenner, Daniel G.; Otten, Gillis R.

doi:10.1073/pnas.90.6.2551

Cited by 63 publications

(21 citation statements)

References 16 publications

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“…To assess the role of B cells, CFSElabeled BALB/c.Thy-1.1 LN cells were injected into irradiated BALB/c.J H Ϫ mice. Because of a deletion in the Ig H chain J region (J H ), these mice are deficient in B cells, but possess normal numbers of polyclonal T cells (10). As shown in Fig.…”

Section: Rapid T Cell Proliferation Is Not Observed In B Cell-deficiementioning

confidence: 99%

Cutting Edge: Recent Immune Status Determines the Source of Antigens That Drive Homeostatic T Cell Expansion

Kieper

Troy²,

Burghardt

et al. 2005

The Journal of Immunology

230

274

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Homeostatic proliferation of naive T cells transferred to T cell-deficient syngeneic mice is driven by low-affinity self-MHC/peptide ligands and the cytokine IL-7. In addition to homeostatic proliferation, a subset of naive T cells undergoes massive proliferation in chronically immunodeficient hosts, but not in irradiated normal hosts. Such rapid T cell proliferation occurs largely independent of homeostatic factors, because it was apparent in the absence of IL-7 and in T cell-sufficient hosts devoid of functional T cell immunity. Strikingly, immunodeficient mice raised under germfree conditions supported only slow homeostatic proliferation, but not the marked T cell proliferation observed in conventionally raised immunodeficient mice. Thus, polyclonal naive T cell expansion in T cell-deficient hosts can be driven predominantly by either self-Ags or foreign Ags depending on the host’s previous state of T cell immunocompetency.

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Section: Rapid T Cell Proliferation Is Not Observed In B Cell-deficiementioning

confidence: 99%

Cutting Edge: Recent Immune Status Determines the Source of Antigens That Drive Homeostatic T Cell Expansion

Kieper

Troy²,

Burghardt

et al. 2005

The Journal of Immunology

230

274

View full text Add to dashboard Cite

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“…Instead of MT mice that have been reported to produce low levels of Ig (29), we chose to use DI mice that are unable to produce mature B cells and Ig due to the knockout of both the heavy and -chain loci (37)(38)(39). Our previous study in DI mice had used B/AA virus.…”

Section: Heterosubtypic Immunity In Ig ϫ/ϫ Micementioning

confidence: 99%

Heterosubtypic Immunity to Influenza A Virus in Mice Lacking IgA, All Ig, NKT Cells, or γδ T Cells

Benton

Misplon

et al. 2001

The Journal of Immunology

126

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The mechanisms of broad cross-protection to influenza viruses of different subtypes, termed heterosubtypic immunity, remain incompletely understood. We used knockout mouse strains to examine the potential for heterosubtypic immunity in mice lacking IgA, all Ig and B cells, NKT cells (CD1 knockout mice), or γδ T cells. Mice were immunized with live influenza A virus and compared with controls immunized with unrelated influenza B virus. IgA−/− mice survived full respiratory tract challenge with heterosubtypic virus that was lethal to controls. IgA−/− mice also cleared virus from the nasopharynx and lungs following heterosubtypic challenge limited to the upper respiratory tract, where IgA has been shown to play an important role. Ig−/− mice controlled the replication of heterosubtypic challenge virus in the lungs. Acute depletion of CD4+ or CD8+ T cell subsets abrogated this clearance of virus, thus indicating that both CD4+ and CD8+ T cells are required for protection in the absence of Ig. These results in Ig−/− mice indicate that CD4+ T cells can function by mechanisms other than providing help to B cells for the generation of Abs. Like wild-type mice, CD1−/− mice and γδ−/− mice survived lethal heterosubtypic challenge. Acute depletion of CD4+ and CD8+ cells abrogated heterosubtypic protection in γδ−/− mice, but not B6 controls, suggesting a contribution of γδ T cells. Our results demonstrate that the Ab and cellular subsets deficient in these knockout mice are not required for heterosubtypic protection, but each may play a role in a multifaceted response that as a whole is more effective than any of its parts.

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“…3 out of 750 ES clones screened were true homologous recombinants. ES cells that were homozygous for the targeted Pkr allele were obtained by selection of the heterozygous targeted clone 7A8.3 in high neomycin selection (2 mg/ml) as described previously (42). Of 20 resistant colonies picked, one clone (7A8.3.7) was homozygous mutant.…”

Section: Construction Of the Pkr Gene-targetingmentioning

confidence: 99%

Characterization of Transgenic Mice with Targeted Disruption of the Catalytic Domain of the Double-stranded RNA-dependent Protein Kinase, PKR

Abraham¹,

Stojdl²,

Duncan³

et al. 1999

Journal of Biological Chemistry

217

178

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The interferon-inducible, double-stranded RNA-dependent protein kinase PKR has been implicated in anti-viral, anti-tumor, and apoptotic responses. Others have attempted to examine the requirement of PKR in these roles by targeted disruption at the amino terminal-encoding region of the Pkr gene. By using a strategy that aims at disruption of the catalytic domain of PKR, we have generated mice that are genetically ablated for functional PKR. Similar to the other mouse model of Pkr disruption, we have observed no consequences of loss of PKR on tumor suppression. Anti-viral response to influenza and vaccinia also appeared to be normal in mice and in cells lacking PKR. Cytokine signaling in the type I interferon pathway is normal but may be compromised in the erythropoietin pathway in erythroid bone marrow precursors. Contrary to the aminoterminal targeted Pkr mouse, tumor necrosis factor ␣-induced apoptosis and the anti-viral apoptosis response to influenza is not impaired in catalytic domain-targeted Pkrnull cells. The observation of intact eukaryotic initiation factor-2␣ phosphorylation in these Pkr-null cells provides proof of rescue by another eukaryotic initiation factor-2␣ kinase(s).

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Analysis of homozygous mutant chimeric mice: deletion of the immunoglobulin heavy-chain joining region blocks B-cell development and antibody production.

Cited by 63 publications

References 16 publications

Cutting Edge: Recent Immune Status Determines the Source of Antigens That Drive Homeostatic T Cell Expansion

Cutting Edge: Recent Immune Status Determines the Source of Antigens That Drive Homeostatic T Cell Expansion

Heterosubtypic Immunity to Influenza A Virus in Mice Lacking IgA, All Ig, NKT Cells, or γδ T Cells

Characterization of Transgenic Mice with Targeted Disruption of the Catalytic Domain of the Double-stranded RNA-dependent Protein Kinase, PKR

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