Immunoglobulin switch circular DNA in the mouse infected with Nippostrongylus brasiliensis: evidence for successive class switching from mu to epsilon via gamma 1.

Yoshida, Kazuya; Matsuoka, Masao; Usuda, S; Mori, A.; Ishizaka, Kimishige; Sakano, Hitoshi

doi:10.1073/pnas.87.20.7829

Cited by 110 publications

(72 citation statements)

References 31 publications

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“…These results suggest that IL-21 increases IgG1 production by the mechanism that is independent from the induction of germ line C␥1 transcription. Regarding the point, Yoshida et al 40 have shown that switch recombination to IgE occurs at least in part in a successive manner: first from IgM to IgG1, and then from IgG1 to IgE. Therefore, it is possible that IL-21 increases IgG1-producing cells through the inhibition of switching from IgG1 to IgE.…”

Section: Discussionmentioning

confidence: 99%

Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cε transcription of IL-4–stimulated B cells

Suto

Nakajima

Hirose

et al. 2002

Blood

210

188

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Interleukin 21 (IL-21) has recently been identified as a multifunctional cytokine that induces the proliferation of T cells and B cells and differentiation of natural killer cells. To determine whether IL-21 regulates IL-4–mediated immune responses, we examined the effect of IL-21 on antigen-specific IgE production in mice. We also examined the effect of IL-21 on IL-4–induced IgE production from B cells and antigen-induced T-helper 2 (Th2) cell differentiation. The in vivo injection of IL-21 prevented antigen-specific IgE but not IgG2a production on immunization. IL-21 did not affect Th2 cell differentiation or IL-4 production from CD4+ T cells but directly inhibited IL-4–induced IgE production from B cells at single-cell levels. Moreover, IL-21 inhibited IL-4–induced germ line Cε transcription in B cells without the inhibition of signal transducer and activator of transcription 6 (Stat6) activation. Taken together, these results indicate that IL-21 down-regulates IgE production from IL-4–stimulated B cells through the inhibition of germ line Cε transcription and thus suggest that IL-21 may be useful for the treatment of IgE-dependent allergic diseases.

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Section: Discussionmentioning

confidence: 99%

Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cε transcription of IL-4–stimulated B cells

Suto

Nakajima

Hirose

et al. 2002

Blood

210

188

View full text Add to dashboard Cite

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“…Molecular analyses of Ig isotype switching support a model of alignment of two switch region sequences which are 5 Ј to each heavy chain region followed by looping out and deletion of the intervening DNA (3). Such excised switch circular DNA has been directly demonstrated in murine (4)(5)(6)(7)(8) and human B cells (9,10). Definitive proof of the ability of a signal to function as an isotype switch factor requires demonstration of it's ability to induce the appropriate deleted switch circular DNA.…”

Section: Introductionmentioning

confidence: 99%

Vasoactive intestinal peptide induces S(alpha)/S(mu) switch circular DNA in human B cells.

Fujieda¹,

Waschek²,

Zhang³

et al. 1996

J. Clin. Invest.

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Vasoactive intestinal peptide (VIP), a major neurotransmitter of peripheral nerves, has been suggested to function in host defense by regulating local human immune function. Indirect evidence has been marshaled that VIP can function as a switch factor for IgA in human Ig isotype recombination. In this study we directly tested the ability of VIP to function as a factor driving human B cells into IgA producing cells by assessing its ability to induce switch circular DNA representing direct to ␣ switching. In addition we determined the generation of

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“…The regulation and existence of IgE memory B cells is controversial and poorly understood (50)(51)(52)(53)(54)(55)(56). It has been suggested that a significant fraction of IgE memory resides in the IgG1 compartment, with generation of a memory IgE response resulting from sequential switching of IgG1 memory B cells to the IgE B cell lineage (50,54,(57)(58)(59)(60)(61)(62)(63)(64). While our studies have not directly addressed this issue, it is interesting that we and others have observed that both primary and memory IgE responses occur prior to IgG1 responses in our immunization and asthma models, perhaps indicating that the vast majority of IgE responses do not develop by a sequential switching mechanism through an IgG1 B cell intermediate.…”

Section: Figurementioning

confidence: 99%

Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice

Brightbill¹,

Jeet²,

Lin³

et al. 2010

J. Clin. Invest.

100

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IgE-mediated hypersensitivity is central to the pathogenesis of asthma and other allergic diseases. Although neutralization of serum IgE with IgE-specific antibodies is in general an efficacious treatment for allergic asthma, one limitation of this approach is its lack of effect on IgE production. Here, we have developed a strategy to disrupt IgE production by generating monoclonal antibodies that target a segment of membrane IgE on human IgE-switched B cells that is not present in serum IgE. This segment is known as the M1′ domain, and using genetically modified mice that contain the human M1′ domain inserted into the mouse IgE locus, we demonstrated that M1′-specific antibodies reduced serum IgE and IgE-producing plasma cells in vivo, without affecting other immunoglobulin isotypes. M1′-specific antibodies were effective when delivered prophylactically and therapeutically in mouse models of immunization, allergic asthma, and Nippostrongylus brasiliensis infection, likely by inducing apoptosis of IgE-producing B cells. In addition, we generated a humanized M1′-specific antibody that was active on primary human cells in vivo, as determined by its reduction of serum IgE levels and IgE plasma cell numbers in a human PBMC-SCID mouse model. Thus, targeting of human IgE-producing B cells with apoptosis-inducing M1′-specific antibodies may be a novel treatment for asthma and allergy.

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Immunoglobulin switch circular DNA in the mouse infected with Nippostrongylus brasiliensis: evidence for successive class switching from mu to epsilon via gamma 1.

Cited by 110 publications

References 31 publications

Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cε transcription of IL-4–stimulated B cells

Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cε transcription of IL-4–stimulated B cells

Vasoactive intestinal peptide induces S(alpha)/S(mu) switch circular DNA in human B cells.

Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice

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