Immunoglobulin heavy chain transgenic mice expressing Galalpha(1,3)Gal-reactive antibodies.

Abstract:

BACKGROUND:Natural antibodies that bind the carbohydrate antigen Galalpha1-3Galbeta1-4GlcNAc-R (alphaGal) mediate rigorous rejection of porcine xenografts and represent a major immunological hurdle to successful discordant xenotransplantation. However, little is known about how production of antibodies specific for alphaGal is regulated. METHODS:Transgenic mice expressing an IgM heavy chain isolated from a B-cell hybridoma that produces antibodies specific for alphaGal were constructed. These mice were bred to mutant mice that lack the alphaGal epitope (GT0 mice) or wild-type (GT+) mice to generate animals in which the transgene is expressed in the presence or absence of alphaGal as a "self"-antigen. Development of transgene-expressing B cells and production of alphaGal-specific serum antibodies were then analyzed in transgenic mice on GT0 and GT+ backgrounds. RESULTS:B cells expressing the transgenic heavy chain and transgene-encoded serum antibodies specific for alphaGal were readily detected in mice on the GT0 background. Most alphaGal-reactive antibodies in GT0 mice used the transgene rather than endogenous Ig heavy chains. In contrast, transgene-encoded serum antibodies specific for alphaGal were not detected in GT+ mice. In transgenic mice on the GT+ background, B cells expressing the transgene underwent deletion as a result of encountering alphaGal during their development, indicating that expression of alphaGal as part of self-mediated efficient negative selection of B cells expressing transgene-encoded alphaGal-specific antibodies. CONCLUSIONS:The development of transgenic mice expressing a B cell receptor specific for alphaGal provides a novel system to study developmental regulation of B cells making carbohydrate-specific antibodies. In addition, these mice may be useful for examining methods to prevent production of alphaGal-reactive antibodies.

journal_name

Transplantation

journal_title

Transplantation

authors

Cretin N,Iacomini J

doi

10.1097/00007890-200205270-00007

subject

Has Abstract

pub_date

2002-05-27 00:00:00

pages

1558-64

issue

10

eissn

0041-1337

issn

1534-6080

journal_volume

73

pub_type

杂志文章
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    pub_type: 杂志文章

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    pub_type: 杂志文章,多中心研究

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    authors: Cibrik DM,Kaplan B,Arndorfer JA,Meier-Kriesche HU

    更新日期:2002-09-15 00:00:00

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    pub_type: 杂志文章

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    更新日期:1998-03-27 00:00:00

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    pub_type: 杂志文章

    doi:

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    authors: Brattström C,Granath F,Edgren G,Smedby KE,Wilczek HE

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    pub_type: 杂志文章

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    更新日期:1993-04-01 00:00:00

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    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

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    pub_type: 杂志文章

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    更新日期:1993-12-01 00:00:00

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    pub_type: 杂志文章

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    authors: Jacobbi LM,McBride VA,Etheredge EE,McDonald JC,Cooper ES,Frey D,Boudreaux JP,Gonzalez F,Van Meter C,McMillan R

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  • Description of B lymphocytes and plasma cells, complement, and chemokines/receptors in acute liver allograft rejection.

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    pub_type: 杂志文章

    doi:10.1097/01.tp.0000132324.14207.8b

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    更新日期:2004-07-15 00:00:00

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    pub_type: 杂志文章

    doi:10.1097/TP.0000000000000054

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    更新日期:2014-08-15 00:00:00

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    更新日期:1995-05-27 00:00:00

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    pub_type: 杂志文章

    doi:10.1097/00007890-197807010-00003

    authors: Lauschke H

    更新日期:1978-07-01 00:00:00

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    pub_type: 杂志文章

    doi:10.1097/00007890-199702270-00012

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    更新日期:1997-02-27 00:00:00