IgG Subclass Determines Suppression Versus Enhancement of Humoral Alloimmunity to Kell RBC Antigens in Mice

Shinde, Paurvi; Howie, Heather L.; Stegmann, Tamara C.; Hay, Ariel; Waterman, Hayley R.; Szittner, Zoltán; Bentlage, Arthur E. H.; Kapp, Linda M.; Lissenberg-Thunnissen, Suzanne N.; Dekkers, Gillian; Schasfoort, Richardus B.M.; Ratcliffe, Sarah J.; Smolkin, Mark E.; Vidarsson, Gestur; Schoot, C. Ellen van der; Hudson, Krystalyn E.; Zimring, James C.

doi:10.3389/fimmu.2020.01516

Cited by 15 publications

(19 citation statements)

References 40 publications

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“…Including this report, this has now repeatedly been observed with 5 different RBC donor strains (HOD, K1, KEL Hi , KEL Med , and KEL Lo ) and three different monoclonal antibodies (anti-K1, anti-Kp b , and anti-HOD). The mechanisms by which IgG2c enhances alloimmunization is unclear; however we have reported that in the case of HOD and K1, Fc gamma receptors on dendritic cells are required (16,17). Moreover, for the HOD system, IgG2c resulted in an increase in proliferation of HOD specific CD4+ T cells.…”

Section: Discussionmentioning

confidence: 93%

“…KEL RBCs). Indirect antiglobulin tests, which also measure antigen-modulation, were carried out by staining with PUMA3 followed by goat-anti-mouse Ig APC and using the same gating strategy (16,17).…”

Section: Determining Post-transfusion Circulation Antibody Binding Tmentioning

confidence: 99%

“…Recently, we have reported that pre-treatment of mice with an IgG2c specific for an RBC antigen can substantially enhance the humoral immune response upon transfusion of RBCs expressing that antigen (16,17). Herein, we tested antigen copy number as an independent variable with regards to how IgG2c affects immune response.…”

Section: Introductionmentioning

confidence: 99%

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Antibodies to Low-Copy Number RBC Alloantigen Convert a Tolerogenic Stimulus to an Immunogenic Stimulus in Mice

et al. 2021

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Red blood cells expressing alloantigens are well known to be capable of inducing robust humoral alloantibody responses both in transfusion and pregnancy. However, the majority of transfusion recipients and pregnant women never make alloantibodies, even after repeat exposure to foreign RBCs. More recently, RBCs have been used as a cellular therapeutic—very much like transfusion, engineered RBCs are highly immunogenic in some cases but not others. In animal models of both transfusion and RBC based therapeutics, RBCs that do not induce an immune response also cause tolerance. Despite a robust phenomenology, the mechanisms of what regulates immunity vs. tolerance to RBCs remains unclear. However, it has been reported that copy number of alloantigens on the RBCs is a critical factor, with a very low copy number causing non-responsiveness (in both humans and mice) and also leading to tolerance in mice. Recently, we reported that an IgG2c specific for an RBC antigen can substantially enhance the humoral immune response upon transfusion of RBCs expressing that antigen. Herein, we report that an IgG2c converts RBCs with low antigen copy number from a tolerogenic to an immunogenic stimulus. These findings report the first known stimulus that induces humoral alloimmunization to a low copy number RBC alloantigen and identify a previously undescribed molecular switch that has the ability to affect responder vs. non-responder phenotypes of transfusion recipients.

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Section: Discussionmentioning

confidence: 93%

Section: Determining Post-transfusion Circulation Antibody Binding Tmentioning

confidence: 99%

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Antibodies to Low-Copy Number RBC Alloantigen Convert a Tolerogenic Stimulus to an Immunogenic Stimulus in Mice

et al. 2021

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“…Another possible explanation for this observation is that the strain of mice used for the study may not be expressing IgG2a. Shinde et al (2020) reported that in some strains of mice there is no expression of IgG2a; instead these mice express the novel IgG2c. Thus, it can be inferred that IgG2a is not a useful immunoglobulin subclass to monitor immune responses to recombinant hepatitis B surface antigen vaccine in non-IgG2a expressing mice.…”

Section: Discussionmentioning

confidence: 99%

Experimental and Molecular Predictions of the Adjuvanticity of Snail Mucin on Hepatitis B Vaccine in Albino Mice

Joshua

Nwauzor

Odimegwu

et al. 2021

Preprint

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Although aluminum-containing adjuvants are widely used in human vaccination due to their excellent safety profile, they exhibit low effectiveness with many recombinant antigens. This study investigated the adjuvanticity of snail mucin with recombinant Hepatitis B Vaccine (rHBsAg). Twenty-five (25) female mice distributed unbiasedly into 5 groups were used in the study and were administered different rHBsAg/Mucin formulation at 7 days intervals. Blood samples were collected a day following the administration for analysis. The results of liver function and body weight analysis were indications that snail mucin had no adverse effect on the mice. The treatment group (administer mucin and rHBsAg) showed significantly (P<0.05) higher mean titres of anti-HBsAg antibodies when compared with the negative controls and the positive control administered with two doses of rHBsAg. Furthermore, a comparable immune response to positive control administered with three doses rHBaAG was recorded. In silico prediction, studies of the protein-protein interaction of a homology modelled snail mucus protein and HBsAg gave an indication of enhanced HBV antigen-antibody interaction. Therefore, this study has shown that snail mucin possesses some adjuvant properties and enhances immune response towards rHBsAg vaccine. However, there is a need for further molecular dynamics studies to understand its mechanism of action.

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“…Another possible explanation for this observation is that the strain of mice used for the study may not be expressing IgG2a. Shinde et al [38] reported that in some strains of mice there is no expression of IgG2a; instead these mice express the novel IgG2c. Thus, it can be inferred that IgG2a is not a useful immunoglobulin subclass to monitor immune responses to recombinant hepatitis B surface antigen vaccine in non-IgG2a expressing mice.…”

Section: Plos Onementioning

confidence: 99%

Experimental and molecular predictions of the adjuvanticity of snail mucin on hepatitis B vaccine in albino mice

et al. 2021

View full text Add to dashboard Cite

Although aluminum-containing adjuvants are widely used in human vaccination due to their excellent safety profile, they exhibit low effectiveness with many recombinant antigens. This study investigated the adjuvanticity of snail mucin with recombinant Hepatitis B Vaccine (rHBsAg). Twenty-five (25) female mice distributed unbiasedly into 5 groups were used in the study and were administered different rHBsAg/Mucin formulation at 7 days intervals. Blood samples were collected a day following the administration for analysis. The results of liver function and body weight analysis were indications that snail mucin had no adverse effect on the mice. The treatment group (administer mucin and rHBsAg) showed significantly (P<0.05) higher mean titres of anti-HBsAg antibodies when compared with the negative controls and the positive control administered with two doses of rHBsAg after the boost doses (day 28). Furthermore, a comparable immune response to positive control administered with three doses rHBaAG was recorded. In silico prediction, studies of the protein-protein interaction of a homology modelled snail mucus protein and HBsAg gave an indication of enhanced HBV antigen-antibody interaction. Therefore, this study has shown that snail mucin possesses some adjuvant properties and enhances immune response towards rHBsAg vaccine. However, there is a need for further molecular dynamics studies to understand its mechanism of action.

show abstract

IgG Subclass Determines Suppression Versus Enhancement of Humoral Alloimmunity to Kell RBC Antigens in Mice

Cited by 15 publications

References 40 publications

Antibodies to Low-Copy Number RBC Alloantigen Convert a Tolerogenic Stimulus to an Immunogenic Stimulus in Mice

Antibodies to Low-Copy Number RBC Alloantigen Convert a Tolerogenic Stimulus to an Immunogenic Stimulus in Mice

Experimental and Molecular Predictions of the Adjuvanticity of Snail Mucin on Hepatitis B Vaccine in Albino Mice

Experimental and molecular predictions of the adjuvanticity of snail mucin on hepatitis B vaccine in albino mice

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