Direct versus sequential immunoglobulin switch in allergy and antiviral responses

Svirshchevskaya, E. V.; Fattakhova, Gulnar; Khlgatian, Svetlana V.; Chudakov, Dmitriy M; Kashirina, E. I.; Ryazantsev, D. Yu.; Kotsareva, Olga Dmitrievna; Завриев, С. К.

doi:10.1016/j.clim.2016.07.022

Cited by 16 publications

(18 citation statements)

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“…Previously we have shown that in young human individuals allergic to house mite dust allergen specific serum IgE production is not associated with production of other Ig classes [1] and may be triggered in sites other than SLOs germinal centers, for example in TLSs. In present study, we demonstrate that model antigen OVA at low dose induces specific IgE production only when administrated in TLSs-enriched region, withers in particular.…”

Section: Discussionmentioning

confidence: 94%

“…For development of the general strategy to eliminate IgE-producing B-cells and their precursors, it is important to know the exact site where B-cell IgE isotype switching occurs. We have previously shown that in young (1-8 years old) patients with allergy to house dust mite specific IgE production is not associated with specific IgG, IgG4 or IgA1 production [1] and may occur outside the germinal centers of secondary lymphoid organs (SLOs), for example, in the tertiary lymphoid structures (TLSs) or so-called tissue-associated lymphoid clusters. Because of the close proximity to epithelial or endothelial barrier tissues immune processes in TLSs may be somewhat different from those in SLOs.…”

Section: Introductionmentioning

confidence: 99%

“…So, in these models, humoral immune response differs from that in allergic patients. Among allergic individuals some of them have significant IgG 4 production [1,10,11] which is not, however, associated with specific IgE levels [1,10,11]. Elevated IgG4 levels detected in atopic patients can represent organism's secondary reaction in response to multiple numbers of antigen entrance.…”

Section: Introductionmentioning

confidence: 99%

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Tertiary lymphoid structures related B-cell IgE isotype switching and secondary lymphoid organs linked IgE production in mouse allergy model

Chudakov

Ryasantsev

Tsaregorotseva³

et al. 2020

Preprint

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Background: Numerous data obtained by different research laboratories around the world indicate that specific IgE production is triggered independently of specific IgG or IgA production and so did not linked to fully matured germinal centers of secondary lymphoid organs. The aim of this study is to clarify whether specific IgE production is triggered by low antigen doses administrated in tertiary lymphoid structure enriched tissues.Methods: OVA in different doses (100 ng or 10 µg) was administrated three times a week for 4–5 weeks intraperitoneally and subcutaneously to female BALB/c mice in the withers region enriched in fat-associated lymphoid clusters and in foot pad region not containing them.Results: OVA-specific IgE was predominantly induced by low but not by high antigen doses and only after immunization in withers. IgE isotype switching was triggered exclusively in withers adipose tissue but not in regional lymph nodes though mature IgE expressing cells were observed both in tissue and lymph nodes. Anti-proliferative genotoxic stress inducing drugs shifted the balance from IgG1 towards IgE production.Conclusion. Tertiary lymphoid structures possess unique environment where B-cell antibody isotype switching to IgE predominantly occurs. These phenomena are explained by hampered proliferation of B-cells in these structures.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tertiary lymphoid structures related B-cell IgE isotype switching and secondary lymphoid organs linked IgE production in mouse allergy model

Chudakov

Ryasantsev

Tsaregorotseva³

et al. 2020

Preprint

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“…Moreover, common lineages in IgG1 + and IgE + B cells have been found in human subjects when analyzing the repertoire of the rearranged immunoglobulin genes ( 117 ), supporting the view that IgE was generated through an indirect switching pathway. In contrast, studies analyzing somatic hypermutation and the correlation between different antibody isotypes in patients with allergies to house dust mite and the fungus Alternaria alternata suggest that IgE is derived through direct switching from IgM to IgE ( 121 ). Moreover, a population of unswitched, IgM + MBCs that have undergone somatic hypermutation have been described in humans ( 122 – 124 ).…”

Section: Ige Immune Responses In Allergymentioning

confidence: 99%

B Cell Responses in the Development of Mammalian Meat Allergy

2020

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Studies of meat allergic patients have shown that eating meat poses a serious acute health risk that can induce severe cutaneous, gastrointestinal, and respiratory reactions. Allergic reactions in affected individuals following meat consumption are mediated predominantly by IgE antibodies specific for galactose-α-1,3-galactose (α-gal), a blood group antigen of non-primate mammals and therefore present in dietary meat. α-gal is also found within certain tick species and tick bites are strongly linked to meat allergy. Thus, it is thought that exposure to tick bites promotes cutaneous sensitization to tick antigens such as α-gal, leading to the development of IgE-mediated meat allergy. The underlying immune mechanisms by which skin exposure to ticks leads to the production of α-gal-specific IgE are poorly understood and are key to identifying novel treatments for this disease. In this review, we summarize the evidence of cutaneous exposure to tick bites and the development of mammalian meat allergy. We then provide recent insights into the role of B cells in IgE production in human patients with mammalian meat allergy and in a novel mouse model of meat allergy. Finally, we discuss existing data more generally focused on tick-mediated immunomodulation, and highlight possible mechanisms for how cutaneous exposure to tick bites might affect B cell responses in the skin and gut that contribute to loss of oral tolerance.

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“…For the development of the general strategy to eliminate IgE-producing B-cells and their precursors, it is important to know the exact site where B-cell IgE isotype switching occurs. We have previously shown that in young (1–8 years old) patients with allergy to house dust mite specific IgE production is not associated with specific IgG, IgG4 or IgA1 production [ 4 ] and may occur outside the germinal centers of secondary lymphoid organs (SLOs). Possibly it can occur in the tertiary lymphoid structures (TLSs) or so-called tissue-associated lymphoid clusters.…”

Section: Introductionmentioning

confidence: 99%

Tertiary lymphoid structure related B-cell IgE isotype switching and secondary lymphoid organ linked IgE production in mouse allergy model

et al. 2020

View full text Add to dashboard Cite

Background Numerous data obtained by different research laboratories indicate that specific IgE production is triggered independently of specific IgG or IgA ones and so it is not linked to fully matured germinal centers formation in the secondary lymphoid organs. The aim of this study was to clarify whether specific IgE production is triggered by low antigen doses administrated in tertiary tissues enriched by lymphoid structures. Methods Ovalbumin (OVA) in different doses (100 ng to 10 μg) was administrated three times a week for 4–5 weeks intraperitoneally (i.p.) or subcutaneously (s.c.) to female BALB/c mice in the wither region which is enriched in fat-associated lymphoid clusters or in the foot pad region not containing them. Results OVA-specific IgE was predominantly induced by low but not high antigen doses and only after immunization into the withers. IgE isotype switching was triggered exclusively in the withers adipose tissue but not in the regional lymph nodes while mature IgE expressing cells were observed both in the withers and lymph nodes. Anti-proliferative genotoxic stress inducing drugs shifted the balance from IgG1 towards IgE production. Conclusions Tertiary lymphoid structures possess unique environment where B-cell antibody isotype switching to IgE predominantly occurs. This phenomenon is partially explained by hampered proliferation of B-cells in these structures.

show abstract

Direct versus sequential immunoglobulin switch in allergy and antiviral responses

Cited by 16 publications

References 50 publications

Tertiary lymphoid structures related B-cell IgE isotype switching and secondary lymphoid organs linked IgE production in mouse allergy model

Tertiary lymphoid structures related B-cell IgE isotype switching and secondary lymphoid organs linked IgE production in mouse allergy model

B Cell Responses in the Development of Mammalian Meat Allergy

Tertiary lymphoid structure related B-cell IgE isotype switching and secondary lymphoid organ linked IgE production in mouse allergy model

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