Deconstructing B cell tolerance to basement membranes

• Authors: M.H. Foster , Y. Zhang , A.G. Clark
• Languages of publication: EN

Abstracts

EN

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 the 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, k 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 the 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.

Keywords

EN

AUTOANTIBODY; B CELL; LAMININ; MEMBRANE; TOLERANCE

Discipline

• IMMUNOLOGY: IMMUNOLOGY

• Publisher: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences
• Journal: Archivum Immunologiae et Therapiae Experimentalis
• Year: 2006
• Volume: 54
• Issue: 4
• Pages: 227-237

Contributors

author

M.H. Foster

author

Y. Zhang

author

A.G. Clark

• Document Type: REVIEW
• Publication order reference: Mary H. Foster, M.D., Department of Medicine, Division of Nephrology, Box 3014, Duke University Medical Center, Durham, NC 27710, USA