Allergen IgE‐isotype‐specific suppression by maternally derived monoclonal anti‐IgG‐idiotype

Tănasă, Radu Iulian; Trad, Ahmad; Lange, Hans; Grötzinger, Joachim; Lemke, Hilmar

doi:10.1111/j.1398-9995.2009.02104.x

Cited by 9 publications

(6 citation statements)

References 42 publications

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“…The importance of controlling the B cell repertoire is underscored by the observation that neonatal injection or maternally derived anti-idiotypic antibodies may induce a drastic distortion of the adult B cell repertoire (20, 21) and maternal anti-idiotypes can even induce a long-lasting transgenerational suppression of IgE responsiveness (22). However, these types of early imprinted responses typically involve B cells expressing specificities directed against antigens encountered early in life.…”

Section: Discussionmentioning

confidence: 99%

Clonal Progression during the T Cell-Dependent B Cell Antibody Response Depends on the Immunoglobulin DH Gene Segment Repertoire

et al. 2014

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The diversity of the third complementarity determining region of the IgH chain is constrained by natural selection of immunoglobulin diversity (DH) sequence. To test the functional significance of this constraint in the context of thymus-dependent (TD) immune responses, we immunized BALB/c mice with WT or altered DH sequence with 2-phenyloxazolone-coupled chicken serum albumin (phOx-CSA). We chose this antigen because studies of the humoral immune response to the hapten phOx were instrumental in the development of the current theoretical framework on which our understanding of the forces driving TD responses is based. To allow direct comparison, we used the classic approach of generating monoclonal Ab (mAb) from various stages of the immune response to phOx to assess the effect of changing the sequence of the DH on clonal expansion, class switching, and affinity maturation, which are hallmarks of TD responses. Compared to WT, TD-induced humoral IgM as well as IgG antibody production in the D-altered ΔD-DμFS and ΔD-iD strains were significantly reduced. An increased prevalence of IgM-producing hybridomas from late primary, secondary, and tertiary memory responses suggested either impaired class switch recombination (CSR) or impaired clonal expansion of class switched B cells with phOx reactivity. Neither of the D-altered strains demonstrated the restriction in the VH/VL repertoire, the elimination of VH1 family-encoded antibodies, the focusing of the distribution of CDR-H3 lengths, or the selection for the normally dominant Ox1 clonotype, which all are hallmarks of the anti-phOx response in WT mice. These changes in clonal selection and expansion, as well as CSR indicate that the genetic constitution of the DH locus, which has been selected by evolution, can strongly influence the functional outcome of a TD humoral response.

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Section: Discussionmentioning

confidence: 99%

Clonal Progression during the T Cell-Dependent B Cell Antibody Response Depends on the Immunoglobulin DH Gene Segment Repertoire

et al. 2014

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“…Several studies [12,28,29,30,31] have demonstrated that maternal allergen-specific IgG, in particular IgG1, may cause suppression of allergen-specific IgE responses in the offspring. If maternal antibodies have this effect, then IgE suppression should wane after weaning when maternal IgG decreases in the offspring’s circulation.…”

Section: Resultsmentioning

confidence: 99%

Early Life Interventions to Prevent Allergy in the Offspring: The Role of Maternal Immunization and Postnatal Mucosal Allergen Exposure

Hansen¹,

Nygaard²,

Lyle³

et al. 2012

Int Arch Allergy Immunol

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Background: Childhood allergy is influenced by maternal factors and allergen exposure in early life, but the factors that determine the development of allergy and tolerance are unknown. Therefore, we compared the effects of two early life interventions, i.e. maternal allergen immunization and postnatal intranasal allergen exposure, as well as a combination of both treatments on allergic responses in the offspring. Methods: Female mice were immunized with ovalbumin (OVA) or vehicle during pregnancy. After birth, half the offspring from each group were exposed intranasally to low doses of OVA or vehicle weekly for 5 weeks before intraperitoneal immunization with OVA. Results: Maternal immunization reduced OVA-specific IgE and IgG1, but increased IgG2a and T_H2 cytokine responses in the offspring after immunization. Postnatal intranasal OVA exposure similarly reduced both IgE and IgG1, but also spleen cell numbers and cytokine secretion. Following airway challenges of the offspring, IgE and airway inflammation were suppressed only by intranasal exposure, but not by maternal immunization, the effect of which also waned with age. Differential gene expression in the spleen of offspring supported that IgE suppression by the two interventions was caused by different mechanisms. Despite this, tolerance development after mucosal exposure was obtained in the offspring of immunized dams. Conclusions: The study suggests that prevention of allergy is possible if initiated in early life, and early mucosal allergen exposure may play a protective role independent of the maternal immune responses.

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“…In a mouse model, the maternally derived anti-id against allergen-specific IgE was shown to induce IgE suppression in the offspring which was long-lasting and dose-dependent. 37 As molecular modeling ruled out an internal image function of the anti-ids, possibly also here the binding to FcγRIIb could contribute to the protective function.…”

Section: The Functional Role Of Anti-ids In Allergymentioning

confidence: 99%

Anti-Ids in Allergy: Timeliness of a Classic Concept

Wallmann

Pali‐Schöll

Jensen‐Jarolim

2010

World Allergy Organization Journal

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Abstract:Anti-idiotypic antibodies (anti-ids) are part of natural immune responses with regulatory capacity. Their effect on an antigen-specific, so-called Ab1 antibody response, is dependent on 1) the original antigen, which they mirror, being Ab2 antibodies, and 2) their isotype. In the case of IgE-mediated allergy, natural anti-ids against allergen-specific IgE represent internal images of allergen molecules. A key biologic feature of allergens is that they can crosslink IgE, expressed by B-lymphocytes or passively bound via high affinity receptors to effector cells, which renders cellular activation. Therefore, the IgE cross linking capability of anti-ids determines whether they dampen or enhance immediate-type hypersensitivity. Correspondingly to classic antiallergen blocking IgG antibodies, anti-ids may also interact with inhibitory FcγRIIb receptors and, thereby, down-regulate TH2-type inflammation. Anti-ids and other B-cell epitope mimetics, like mimotopes and DARPins, represent antigen surrogates, which can be used for vaccination. Intriguingly, they may induce antibody responses without activating potentially proinflammatory, antiallergen T-lymphocytes. Taken together, collective evidence suggests that anti-ids, although representing immunologic classics, are a timeless concept in allergology.

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Allergen IgE‐isotype‐specific suppression by maternally derived monoclonal anti‐IgG‐idiotype

Cited by 9 publications

References 42 publications

Clonal Progression during the T Cell-Dependent B Cell Antibody Response Depends on the Immunoglobulin DH Gene Segment Repertoire

Clonal Progression during the T Cell-Dependent B Cell Antibody Response Depends on the Immunoglobulin DH Gene Segment Repertoire

Early Life Interventions to Prevent Allergy in the Offspring: The Role of Maternal Immunization and Postnatal Mucosal Allergen Exposure

Anti-Ids in Allergy: Timeliness of a Classic Concept

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