Transfusion of antibody‐opsonized red blood cells results in a shift in the immune response from the red blood cell to the antibody in a murine model

Brinc, Davor; Le-Tien, Hoang; Crow, Andrew R.; Semple, John W.; Freedman, John; Lazarus, Alan H.

doi:10.1111/j.1537-2995.2010.02645.x

Cited by 15 publications

(16 citation statements)

References 52 publications

(61 reference statements)

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“…In the AMID work, mice were injected with SRBCs or the diphtheria/ tetanus vaccine in the presence versus absence of Ag-specific IgG. We observed that under conditions in which the IgG successfully mediated an AMIS effect against the Ag, a dose-dependent humoral immune response against the AMIS-inducing IgG was observed (5). These Abs (anti-IgG) observed in our prior work somewhat resemble rheumatoid-like factors, which may themselves be immune regulatory, or their appearance could simply be an indication of immune deviation away from the original Ag.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, a variety of other hypotheses can explain AMIS induction (Table I). Although any of these hypotheses could potentially be responsible for AMIS effects, our recent finding of AMID being related to AMIS induction is of interest (5). In the AMID work, mice were injected with SRBCs or the diphtheria/ tetanus vaccine in the presence versus absence of Ag-specific IgG.…”

Section: Discussionmentioning

confidence: 99%

“…To detect IgM and IgG subclasses specific for HEL or OVA, an ELISAbased assay was used as previously described (5). Briefly, ELISA plates were coated with 10 mg/ml HEL or OVA in PBS.…”

Section: Detection Of the Hod-specific Ab Responsementioning

confidence: 99%

“…The Ab response to RBCs can be downregulated by the simultaneous administration of an RBC-specific Ab concurrent with exposure to the foreign red cell (1)(2)(3)(4). This effect has been termed Ab-mediated immune suppression (AMIS), and AMIS has been observed with a variety of different cell types, including platelets, leukocytes, microbes, and particulate Ags, such as vaccines in different mammals (5)(6)(7)(8).…”

mentioning

confidence: 99%

“…Although not universally agreed upon, the most commonly accepted theories to explain the AMIS effect with erythrocytes are 1) that the AMIS Ab is able to rapidly clear Ag-positive target cells before they can be recognized by the immune system (10-12, 16, 17), theoretically based on FcgRmediated phagocytosis of D + RBCs preventing B cells from recognizing the D Ag (10,11,17), or 2) that the AMIS Ab sterically hinders the ability of the immune response to see or detect the Ag (4,15,16,18). Other theories with direct experimental support have suggested that inhibition may occur through the inhibitory FcgRIIB (19), that inhibitory cytokines may be produced (20), that glycosylation of the AMIS Ab may play a role (21)(22)(23), and/or that Abmediated immune deviation (AMID) away from the Ag and directed toward the sensitizing Ab may be involved (5). In addition to these theories, a number of others have been proposed (Table I).…”

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confidence: 99%

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Antibody-Mediated Immune Suppression of Erythrocyte Alloimmunization Can Occur Independently from Red Cell Clearance or Epitope Masking in a Murine Model

Stowell

Bernardo

et al. 2014

The Journal of Immunology

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Anti-D can prevent immunization to the RhD Ag on RBCs, a phenomenon commonly termed Ab-mediated immune suppression (AMIS). The most accepted theory to explain this effect has been the rapid clearance of RBCs. In mouse models using SRBC, these xenogeneic cells are always rapidly cleared even without Ab, and involvement of epitope masking of the SRBC Ags by the AMIS-inducing Ab (anti-SRBC) has been suggested. To address these hypotheses, we immunized mice with murine transgenic RBCs expressing the HOD Ag (hen egg lysozyme [HEL], in sequence with ovalbumin, and the human Duffy transmembrane protein) in the presence of polyclonal Abs or mAbs to the HOD molecule. The isotype, specificity, and ability to induce AMIS of these Abs were compared with accelerated clearance as well as steric hindrance of the HOD Ag. Mice made IgM and IgG reactive with the HEL portion of the molecule only. All six of the mAbs could inhibit the response. The HEL-specific Abs (4B7, IgG1; GD7, IgG2b; 2F4, IgG1) did not accelerate clearance of the HOD-RBCs and displayed partial epitope masking. The Duffy-specific Abs (MIMA 29, IgG2a; CBC-512, IgG1; K6, IgG1) all caused rapid clearance of HOD RBCs without steric hindrance. To our knowledge, this is the first demonstration of AMIS to erythrocytes in an all-murine model and shows that AMIS can occur in the absence of RBC clearance or epitope masking. The AMIS effect was also independent of IgG isotype and epitope specificity of the AMIS-inducing Ab.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…To detect IgM and IgG subclasses specific for HEL or OVA, an ELISAbased assay was used as previously described (5). Briefly, ELISA plates were coated with 10 mg/ml HEL or OVA in PBS.…”

Section: Detection Of the Hod-specific Ab Responsementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Antibody-Mediated Immune Suppression of Erythrocyte Alloimmunization Can Occur Independently from Red Cell Clearance or Epitope Masking in a Murine Model

Stowell

Bernardo

et al. 2014

The Journal of Immunology

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Application of anti-D immunoglobulin in D-negative pregnant women in China

Fu,

Ma,

2024

Transfusion Clinique et Biologique

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IgG-mediated immune suppression in mice is epitope specific except during high epitope density conditions

Zhang

Heyman

2018

Sci Rep

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Specific IgG antibodies, passively administered together with erythrocytes, suppress antibody responses against the erythrocytes. Although used to prevent alloimmunization in Rhesus (Rh)D-negative women carrying RhD-positive fetuses, the mechanism behind is not understood. In mice, IgG suppresses efficiently in the absence of Fcγ-receptors and complement, suggesting an Fc-independent mechanism. In line with this, suppression is frequently restricted to the epitopes to which IgG binds. However, suppression of responses against epitopes not recognized by IgG has also been observed thus arguing against Fc-independence. Here, we explored the possibility that non-epitope specific suppression can be explained by steric hindrance when the suppressive IgG binds to an epitope present at high density. Mice were transfused with IgG anti-4-hydroxy-3-nitrophenylacetyl (NP) together with NP-conjugated sheep red blood cells (SRBC) with high, intermediate, or low NP-density. Antibody titers and the number of single antibody-forming cells were determined. As a rule, IgG suppressed NP- but not SRBC-specific responses (epitope specific suppression). However, there was one exception: suppression of both IgM anti-SRBC and IgM anti-NP responses occurred when high density SRBC-NP was administered (non-epitope specific suppression). These findings answer a longstanding question in antibody feedback regulation and are compatible with the hypothesis that epitope masking explains IgG-mediated immune suppression.

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Transfusion of antibody‐opsonized red blood cells results in a shift in the immune response from the red blood cell to the antibody in a murine model

Abstract: This work demonstrates that, under AMIS conditions, the IgG itself becomes the focus of B cells in the immune system, suggesting a potential mechanism of B-cell regulation.

Cited by 15 publications

References 52 publications

Antibody-Mediated Immune Suppression of Erythrocyte Alloimmunization Can Occur Independently from Red Cell Clearance or Epitope Masking in a Murine Model

Antibody-Mediated Immune Suppression of Erythrocyte Alloimmunization Can Occur Independently from Red Cell Clearance or Epitope Masking in a Murine Model

Application of anti-D immunoglobulin in D-negative pregnant women in China

IgG-mediated immune suppression in mice is epitope specific except during high epitope density conditions

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