Deconstructing B cell tolerance to basement membranes.

Deconstructing B cell tolerance to basement membranes. Research Abstract Details 

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Deconstructing B cell tolerance to basement membranes. Abstract Text:

Mary H Foster,Ying Zhang,Amy G Clark,

Basement membrane antigens are frequent targets of autoantibody attack in systemic and organ-restricted autoimmunity. These specialized and highly organized matrices are composed of multiple components with restricted tissue distributions and limited epitope exposure. To dissect mechanisms controlling humoral autoimmunity to nephritogenic basement membrane antigens, we developed autoantibody transgenic models. In mice bearing the LamH Ig transgene encoding B cell receptors specific for laminin, autoreactive B cells are readily generated but actively regulated in vivo. In this model, anti-laminin B cells are immunologically censored by mechanisms that include central deletion, kappa light-chain editing, and anergy. Tolerance is maintained when the transgene is established in MRL and BXSB genetic backgrounds with inherited autoimmune susceptibility, and despite provocation with potent environmental stimulants. Collectively, these studies indicate that the pathogenic anti-laminin reactivity characteristic of systemic lupus is tightly regulated. A novel anti-collagen transgenic model is used to assess the tolerogenesis of a structurally distinct pathogenic basement membrane epitope and to determine if reactivity to putative cryptic epitopes targeted in organ-restricted disease is regulated. These studies should provide insight into the molecular mechanisms controlling basement membrane autoreactivity and ultimately facilitate the development of novel strategies to inactivate autoreactive cells and treat autoimmune disease.

Deconstructing B cell tolerance to basement membranes. Publishing Authors By Initials

MH Foster,Y Zhang,AG Clark,

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Deconstructing B cell tolerance to basement membranes. Journal Published:

PUBLICATION TYPE: Review

Journal: Archivum immunologiae et therapiae experimentalis

VOLUME: 54

Page Numbers: 227-37

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ISSN: 0004-069X

DAY: 10

MONTH: 07

YEAR: 2006

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LANGUAGE: eng

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Grant and Affiliation Information for Deconstructing B cell tolerance to basement membranes.

AFFILIATION: Department of Medicine, Duke University, Durham Veterans Affairs Medical Centers, Durham, NC 27710, USA. mhfoster@duke.edu

Country: Switzerland

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MEDLINETA: Arch Immunol Ther Exp (Warsz)

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