CD4+ T cell responses in mice lacking MHC class II molecules specifically on B cells

Williams, G. Stuart; Oxenius, Annette; Hengartner, Hans; Benoist, Christophe; Mathis, Diane

doi:10.1002/(sici)1521-4141(199811)28:11<3763::aid-immu3763>3.0.co;2-d

Cited by 29 publications

(21 citation statements)

References 53 publications

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“…Thus, B cells may contribute to the full expansion of Ag-specific CD4 T cells to drive Th2 differentiation, but whether this requires Ag presentation is controversial (12)(13)(14). However, the effects of B cell Ag presentation on Th1 CD4 ϩ differentiation are unknown.…”

Section: T Cells In the Thymus And Function To Present Peptide Ags Tosupporting

confidence: 91%

“…Because isotype switching requires cognate interactions between activated CD4 T cells and Ag-specific B cells (14,45), the level of anti-OVA IgG in the serum 13 days after immunization was measured. As expected, no OVA-specific IgG was detected in the absence of cognate Ag or MHCII, whereas wild-type I-A ␤ b ϩ/Ϫ mice immunized with OVA protein and LPS had elevated titers of specific Abs.…”

Section: In Vivo Presentation Of Protein Agsmentioning

confidence: 99%

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CD8α+ and CD11b+ Dendritic Cell-Restricted MHC Class II Controls Th1 CD4+ T Cell Immunity

Lemos

Fan

et al. 2003

The Journal of Immunology

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The activation, proliferation, differentiation, and trafficking of CD4 T cells is central to the development of type I immune responses. MHC class II (MHCII)-bearing dendritic cells (DCs) initiate CD4+ T cell priming, but the relative contributions of other MHCII+ APCs to the complete Th1 immune response is less clear. To address this question, we examined Th1 immunity in a mouse model in which I-Aβb expression was targeted specifically to the DCs of I-Aβb−/− mice. MHCII expression is reconstituted in CD11b+ and CD8α+ DCs, but other DC subtypes, macrophages, B cells, and parenchymal cells lack of expression of the I-Aβb chain. Presentation of both peptide and protein Ags by these DC subsets is sufficient for Th1 differentiation of Ag-specific CD4+ T cells in vivo. Thus, Ag-specific CD4+ T cells are primed to produce Th1 cytokines IL-2 and IFN-γ. Additionally, proliferation, migration out of lymphoid organs, and the number of effector CD4+ T cells are appropriately regulated. However, class II-negative B cells cannot receive help and Ag-specific IgG is not produced, confirming the critical MHCII requirement at this stage. These findings indicate that DCs are not only key initiators of the primary response, but provide all of the necessary cognate interactions to control CD4+ T cell fate during the primary immune response.

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Section: T Cells In the Thymus And Function To Present Peptide Ags Tosupporting

confidence: 91%

Section: In Vivo Presentation Of Protein Agsmentioning

confidence: 99%

CD8α+ and CD11b+ Dendritic Cell-Restricted MHC Class II Controls Th1 CD4+ T Cell Immunity

Lemos

Fan

et al. 2003

The Journal of Immunology

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“…However, B cells can influence T cell function through a variety of means (21,(34)(35)(36)(37)(38). It has been suggested that they are involved in regulating the activation status and number of effector T lymphocytes based on observations of abnormal CD4 ϩ T cell responses in B cell-deficient mice (36, 37).…”

Section: Discussionmentioning

confidence: 99%

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

Gavanescu

Benoist

Mathis

2008

Proc. Natl. Acad. Sci. U.S.A.

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Autoimmune regulator (Aire)-deficient mice and humans have circulating autoantibodies against a multitude of organs and multiorgan autoinflammatory infiltrates. It is not known to what extent autoantibodies or their source, B lymphocytes, are required for disease onset or progression. We show in this research that B cells must be present for Aire-deficient mice to develop fulminant infiltrates. We found no evidence that autoantibodies were directly pathogenic; rather, B cells appeared to play a critical early role in T cell priming or expansion. A therapeutic reagent directed against B cells, Rituximab, induced remission of the autoimmune disease in Aire-deficient mice, raising the hope of applying it to human patients with autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).autoimmunity ͉ B lymphocytes ͉ tolerance ͉ autoantibody

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“…Our data suggest that germinal center formation involves quantitatively (or qualitatively) more stringent T cell-B cell interactions than the interactions resulting in Ig subclass switching. It is unlikely that the IgG production in these mice reflects bystander activation of B cells as a result of T cell priming by dendritic cells, since IgG production after OVA immunization requires Ag presentation by the B cells themselves (35) The Ab response after immunization prompted us to analyze Ag presentation in more detail. Different epitopes from a single Ag may display different DM requirements (14,28), and it was possible that one or several epitopes were still presented relatively efficiently by DM-deficient APCs.…”

Section: Discussionmentioning

confidence: 99%

The Impact of H2-DM on Humoral Immune Responses

Alfonso¹,

Han²,

Williams³

et al. 2001

The Journal of Immunology

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H2-DM (DM, previously H2-M) facilitates the exchange of peptides bound to MHC class II molecules. In this study, we have used H2-DM-deficient (DM−/−) mice to analyze the influence of DM in the priming of B cell responses in vivo and for Ag presentation by B cells in vitro. After immunization, IgG Abs could be raised to a T-dependent Ag, 4-hydroxy-5-nitrophenylacetyl-OVA, in DM−/− mice, but closer analysis revealed the IgG response to be slower, diminished in titer, and composed of low-affinity Abs. The Ab response correlated with a vast reduction in the number of germinal centers in the spleen. The presentation of multiple epitopes by H2-Ab from distinct Ags was found to be almost exclusively DM-dependent whether B cells internalized Ags via fluid phase uptake or using membrane Ig receptors. The poor B cell response in vivo could be largely, but not completely restored by expression of a H2-Ead transgene, despite the fact that Ag presentation by H2-Ed/b molecules was found to be highly DM dependent. Hence, while substantial Ab responses can be raised in the absence of DM, this molecule is a crucial factor both for Ag processing and for the normal maturation of T-dependent humoral immune responses in vivo.

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CD4+ T cell responses in mice lacking MHC class II molecules specifically on B cells

Cited by 29 publications

References 53 publications

CD8α+ and CD11b+ Dendritic Cell-Restricted MHC Class II Controls Th1 CD4+ T Cell Immunity

CD8α+ and CD11b+ Dendritic Cell-Restricted MHC Class II Controls Th1 CD4+ T Cell Immunity

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

The Impact of H2-DM on Humoral Immune Responses

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