B-cell anergy is maintained in anti-DNA transgenic NZB/NZW mice.

Clonal anergy has been well recognized as an important mechanism of B cell immunologic tolerance. However, the properties of anergic B cells and especially their role in the development of autoimmune disease in susceptible animals have been controversial. Here we show that low-affinity anti-DNA anergic B cells populate the mature B-cell compartment in the mouse spleen in excessive numbers and display paradoxical behavior in response to a combined B-cell receptor/TLR9 activation.

Autoreactive anti-DNA transgenic B cells in lupus-prone New Zealand black/New Zealand white mice show near perfect L chain allelic exclusion.

Recent work on B cell tolerance and autoimmunity has suggested the L chain allelic inclusion is a property of autoreactive B cells and is closely linked to receptor editing. Allelic inclusion could rescue autoreactive B cells from clonal deletion by reducing their effective BCR surface density. We have investigated this phenomenon in anti-DNA producing hybridomas, derived from different strains of Ig gene-targeted, lupus-prone NZB/NZW mice.

Peripheral B cell receptor editing may promote the production of high-affinity autoantibodies in CD22-deficient mice.

CD22-deficient mice are characterized by B cell hyperactivity and autoimmunity. We have constructed knock-in CD22-/- mice, expressing an anti-DNA heavy (H) chain (D42), alone or combined with Vkappa1-Jkappa1 or Vkappa8-Jkappa5 light (L) chains. The Ig-targeted mice produced a lupus-like serology that was age- and sex-dependent.

The effects of colchicine and hydroxychloroquine on the cyclo-oxygenases COX-1 and COX-2.

Objective: The aim of this study was to test whether colchicine and hydroxychloroquine have an inhibitory effect on cyclo-oxygenases (COX).

Methods: Measurement of COX-1 and COX-2 activity was performed by using whole blood assay. Serum thromboxane (TXA) and plasma prostaglandin 2 (PGE2) levels were determined using a commercially available enzyme immunoassay kit.

Autoimmune NZB/NZW F1 mice utilize B cell receptor editing for generating high-affinity anti-dsDNA autoantibodies from low-affinity precursors.

We have previously constructed knock-in (C57BL/6xBALB/c) F1 mice, each expressing an anti-DNA heavy (H) chain (D42), combined with one of three different light (L) chains, namely Vkappa1-Jkappa1, Vkappa4-Jkappa4 or Vkappa8-Jkappa5. All of these H/L chain combinations bind DNA with similar affinity and fine specificity. However, while mice carrying Vkappa1-Jkappa1-transgenic L chain were tolerized almost exclusively by L chain receptor editing, the mice expressing Vkappa8-Jkappa5 L chains utilized clonal anergy as their principal mechanism of B cell tolerance.