Development and characterization of anti-Gal B cell receptor transgenic Gal???/??? mice

Xu, Hui; Sharma, Ajay; Lei, Ying; Okabe, Jeannine; Wan, Hua‐Ping; Chong, Anita S.; Logan, John S.; Byrne, Guerard W.

doi:10.1097/00007890-200205270-00006

Cited by 11 publications

(14 citation statements)

References 43 publications

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“…Characterization of B cell development in the bone marrow of M86V H V L GT 0/0 or M86V H V L GT ϩ/ϩ knock-in mice demonstrated that pro-B cells (B220 ϩ ,CD43 ϩ ) and immature (B220 ϩ ,CD43 Ϫ ) B cells, as defined in (48,49), were present in similar proportions to those observed in normal mice, although the frequency of each of these fractions was reduced when compared with normal controls (Fig. 2A), as observed in other Ig knock-in mice (32,33). The frequency of pre-B cells was similar in M86V H V L GT 0/0 or M86V H V L GT ϩ/ϩ knock-in mice (data not shown).…”

Section: Characterization Of Early Lymphocyte Development In M86v H Vsupporting

confidence: 58%

“…However, the frequency of B cells producing ␣Gal specific Abs in these mice is too low to allow for their direct analysis. We and others have previously attempted to overcome this difficulty by generating Ig transgenic mice that express transgenes encoding ␣Gal-specific Abs (32,33). However, these models are limited because the expressed transgenes were not subject to regulation by elements within the endogenous Ig loci, making it difficult to assess physiological relevance.…”

Section: Discussionmentioning

confidence: 99%

“…Using Ig transgenic mice, it has been suggested previously that B cells producing ␣Gal-specific Abs are skewed to a MZ B cell phenotype (33). However, the use of Ig transgenic mice has made it difficult to determine whether this observation is of physiological relevance.…”

Section: Discussionmentioning

confidence: 99%

“…However, the frequency of B cells that produce ␣Gal-specific Abs in these mice is low, making direct analysis of B cells producing ␣Gal-specific Abs difficult. We and others have generated Ig transgenic mice to study regulation of B cells producing ␣Gal-specific Abs (32,33). However, the use of these mice to address several aspect of B cell development is limited because the Ig transgenes are randomly integrated.…”

mentioning

confidence: 99%

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Ig Knock-In Mice Producing Anti-Carbohydrate Antibodies: Breakthrough of B Cells Producing Low Affinity Anti-Self Antibodies

Benatuil

Kaye

Crétin

et al. 2008

The Journal of Immunology

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Natural Abs specific for the carbohydrate Ag Galα1–3Galβ1–4GlcNAc-R (αGal) play an important role in providing protective host immunity to various pathogens; yet little is known about how production of these or other anti-carbohydrate natural Abs is regulated. In this study, we describe the generation of Ig knock-in mice carrying functionally rearranged H chain and L chain variable region genes isolated from a B cell hybridoma producing αGal-specific IgM Ab that make it possible to examine the development of B cells producing anti-carbohydrate natural Abs in the presence or absence of αGal as a self-Ag. Knock-in mice on a αGal-deficient background spontaneously developed αGal-specific IgM Abs of a sufficiently high titer to mediate rejection of αGal expressing cardiac transplants. In the spleen of these mice, B cells expressing αGal-specific IgM are located in the marginal zone. In knock-in mice that express αGal, B cells expressing the knocked in BCR undergo negative selection via receptor editing. Interestingly, production of low affinity αGal-specific Ab was observed in mice that express αGal that carry two copies of the knocked in H chain. We suggest that in these mice, receptor editing functioned to lower the affinity for self-Ag below a threshold that would result in overt pathology, while allowing development of low affinity anti-self Abs.

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Section: Characterization Of Early Lymphocyte Development In M86v H Vsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Ig Knock-In Mice Producing Anti-Carbohydrate Antibodies: Breakthrough of B Cells Producing Low Affinity Anti-Self Antibodies

Benatuil

Kaye

Crétin

et al. 2008

The Journal of Immunology

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“…For complement activation, the cells were washed and then incubated with a 1/10 dilution of mouse serum and FITCconjugated anti-mouse C3b (Cappel-Organon Teknika, Durham, NC) or goat anti-sera to human-C5 (Quidel), biotin-conjugated rabbit anti-goat IgG (Vector Laboratories, Burlingame, CA), and streptavidin-FITC (BD PharMingen, San Diego, CA). Anti-Gal mAbs were also assayed for the ability to cause complement-mediated lysis with a hemoglobin release assay as previously reported (10 Received for publication March 1, 2004. Accepted for publication April 16, 2004.…”

Section: Binding and Complement Activation By Anti-gal Mabsmentioning

confidence: 99%

Cutting Edge: NK Cells Mediate IgG1-Dependent Hyperacute Rejection of Xenografts

Yin

Zeng

et al. 2004

The Journal of Immunology

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Classic hyperacute rejection is dependent on the activation of the terminal components of complement. Recently, xenoantibodies with limited abilities to activate the classical pathway of complement in vitro have been implicated in the acute vascular rejection of xenografts. It is unclear how these Abs affect their pathogenic activities in vivo. In this study, we demonstrate the ability of an anti-Gal-α1,3Gal (Gal) IgG1, with modest complement-activating abilities in vitro, to induce xenograft rejection. This rejection was dependent on the activation of complement, on FcγR-mediated interactions, and on the presence of NK cells. Inhibition of any one of these factors resulted in the abrogation of IgG1-mediated rejection. In contrast, an anti-Gal IgG3 mAb induced classic, hyperacute rejection that was solely dependent on complement activation. Our observations implicate two types of IgG-mediated rejection; one that is dependent on complement activation, and a second that is uniquely dependent on complement, FcγR, and NK cells.

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The influence of natural antibody specificity on antigen immunogenicity

et al. 2005

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The natural antibody repertoire in humans, apes and Old World primates is distinct from the repertoire of all other placental mammals, and encodes antibodies specific for the carbohydrate epitope Galα1–3Galβ1–4GlcNAc‐R (αGal). Here, we examined whether conjugating antigens to the αGal epitope can augment their immunogenicity in α(1,3)galactosyltransferase knockout mice (GT0 mice) which, like humans, produce αGal‐specific antibodies. Immunization of GT0 mice with BSA conjugated to αGal (αGal‐BSA) led to significant production of anti‐BSA IgG antibodies without the need for adjuvant. This response was dependent on the presence of αGal‐reactive antibodies. Immunization of wild‐type mice with αGal‐BSA failed to induce an anti‐BSA response. The presence of αGal‐reactive antibodies also led to an increase in the T cell response to BSA following immunization with αGal‐BSA when compared with mice that received BSA alone, resulting in an increased frequency of IFN‐γ− and IL‐4‐producing BSA‐specific T cells. In addition, the ability to produce αGal‐reactive antibodies enhanced the cytotoxic T lymphocyte anti‐viral antigen response following vaccination with murine leukemia virus transformed cell lines that express αGal on their cell surface. Natural antibodies that bind αGal therefore play a key role in increasing the efficiency of priming to antigens decorated with αGal epitopes.

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Development and characterization of anti-Gal B cell receptor transgenic Gal???/??? mice

Abstract: These observations suggest that this model can be used to study the regulation of anti-Gal B cells and can establish a reliable source of functional anti-Gal B cells, which could be used to test the effectiveness of alpha-Gal-specific immunosuppressive reagents.

Cited by 11 publications

References 43 publications

Ig Knock-In Mice Producing Anti-Carbohydrate Antibodies: Breakthrough of B Cells Producing Low Affinity Anti-Self Antibodies

Ig Knock-In Mice Producing Anti-Carbohydrate Antibodies: Breakthrough of B Cells Producing Low Affinity Anti-Self Antibodies

Cutting Edge: NK Cells Mediate IgG1-Dependent Hyperacute Rejection of Xenografts

The influence of natural antibody specificity on antigen immunogenicity

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