Regulation of basement membrane-reactive B cells in BXSB, (NZBxNZW)F1, NZB, and MRL/lpr lupus mice.

Autoantibodies to diverse antigens escape regulation in systemic lupus erythematosus under the influence of a multitude of predisposing genes. To gain insight into the differential impact of diverse genetic backgrounds on tolerance mechanisms controlling autoantibody production in lupus, we established a single lupus-derived nephritis associated anti-basement membrane Ig transgene on each of four inbred murine lupus strains, including BXSB, (NZBxNZW)F1, NZB, and MRL/lpr, as approved by the Duke University and the Durham Veterans Affairs Medical Centers' Animal Care and Use Committees. In nonautoimmune C57BL/6 mice, B cells bearing this anti-laminin Ig transgene are stringently regulated by central deletion, editing, and anergy.

Genetic elimination of α3(IV) collagen fails to rescue anti-collagen B cells.

Organ deposition of autoantibodies against the noncollagenous-1 domain of the α3 chain of type IV collagen leads to severe kidney and lung injury in anti-glomerular basement membrane disease. The origin and regulation of these highly pathogenic autoantibodies remains unknown. Anti-α3(IV) collagen B lymphocytes are predicted to mature in vivo ignorant of target antigen because α3(IV) collagen expression is highly tissue restricted and pathogenic epitopes are cryptic.

Central tolerance regulates B cells reactive with Goodpasture antigen alpha3(IV)NC1 collagen.

Patients and rodents with Goodpasture's syndrome (GPS) develop severe autoimmune crescentic glomerulonephritis, kidney failure, and lung hemorrhage due to binding of pathogenic autoantibodies to the NC1 domain of the alpha3 chain of type IV collagen. Target epitopes are cryptic, normally hidden from circulating Abs by protein-protein interactions and the highly tissue-restricted expression of the alpha3(IV) collagen chain. Based on this limited Ag exposure, it has been suggested that target epitopes are not available as B cell tolerogens.

Tracking Differential Gene Expression in MRL/MpJ Versus C57BL/6 Anergic B Cells: Molecular Markers of Autoimmunity.

BACKGROUND: Anergy is a key mechanism controlling expression of autoreactive B cells and a major site for failed regulation in autoimmune diseases. Yet the molecular basis for this differentiated cell state remains poorly understood. The current lack of well-characterized surface or molecular markers hinders the isolation of anergic cells for further study.

Effects of dietary phytase on body weight gain, body composition and bone strength in growing rats fed a low-zinc diet.

Phytic acid, a major phosphorous storage compound found in foodstuffs, is known to form insoluble complexes with nutritionally essential minerals, including zinc (Zn). Phytases are enzymes that catalyze the removal of these minerals from phytic acid, improving their bioavailability. The objective of the present study was to determine the ability of dietary phytase to affect body weight, body composition, and bone strength in growing rats fed a high phytic acid, low Zn diet.