B Cell Tolerance and Positive Selection in Lupus

B cell tolerance and positive selection in lupus.

Systemic lupus erythematosus is considered a prototype of systemic autoimmune diseases; however, despite considerable advances in recent years in the understanding of basic mechanisms in immunology, little progress has been made in elucidating the etiology and pathogenesis of this disease. This even holds for inbred mice, such as the lupus-prone New Zealand Black/New Zealand White F(1) mice, wh...

Defective B cell tolerance checkpoints in systemic lupus erythematosus

A cardinal feature of systemic lupus erythematosus (SLE) is the development of autoantibodies. The first autoantibodies described in patients with SLE were those specific for nuclei and DNA, but subsequent work has shown that individuals with this disease produce a panoply of different autoantibodies. Thus, one of the constant features of SLE is a profound breakdown in tolerance in the antibody...

B-cell tolerance checkpoint violations in systemic lupus erythematosus

Increased positive selection of B1 cells and reduced B cell tolerance to intracellular antigens in c1q-deficient mice.

Inherited deficiency of early components of the classical complement pathway is strongly associated with the targeting of intracellular self Ags in systemic lupus erythematosus, but the reasons for this association are debated. In this study, we show that C1q deficiency increases the positive selection of B1b B cells and IgM autoantibodies by an intracellular self Ag, which is exposed on dying ...

Importance of spliceosomal RNP1 motif for intermolecular T-B cell spreading and tolerance restoration in lupus

We previously demonstrated the importance of the RNP1 motif-bearing region 131-151 of the U1-70K spliceosomal protein in the intramolecular T-B spreading that occurs in MRL/lpr lupus mice. Here, we analyze the involvement of RNP1 motif in the development and prevention of naturally-occurring intermolecular T-B cell diversification. We found that MRL/lpr peripheral blood lymphocytes proliferated...