scholarly journals Balancing diversity and tolerance

2005 ◽  
Vol 202 (3) ◽  
pp. 341-344 ◽  
Author(s):  
Annett M. Jacobi ◽  
Betty Diamond
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Tolerance ◽  
Systemic Lupus ◽  
Cell Repertoire ◽  
B Cell Tolerance ◽  
Repertoire Selection ◽  
B Cell Repertoire ◽  
Disease Systemic Lupus Erythematosus

The autoimmune disease systemic lupus erythematosus (SLE) is caused by a failure of B cell tolerance. Recent studies in mouse models of SLE have identified several distinct tolerance checkpoints that must each function appropriately to protect against disease. However, studies of B cell repertoire selection in humans are essential to understand which checkpoints are defective in human autoimmune diseases.

scholarly journals Defective B cell tolerance checkpoints in systemic lupus erythematosus

2005 ◽  
Vol 201 (5) ◽  
pp. 703-711 ◽  
Author(s):  
Sergey Yurasov ◽  
Hedda Wardemann ◽  
Johanna Hammersen ◽  
Makoto Tsuiji ◽  
Eric Meffre ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Tolerance ◽  
Systemic Lupus ◽  
Cell Repertoire ◽  
B Cell Tolerance ◽  
Subsequent Work ◽  
Healthy Humans ◽  
B Cell Repertoire

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 system. The appearance of self-reactive antibodies in SLE precedes clinical disease, but where in the B cell pathway tolerance is first broken has not been defined. In healthy humans, autoantibodies are removed from the B cell repertoire in two discrete early checkpoints in B cell development. We found these checkpoints to be defective in three adolescent patients with SLE. 25–50% of the mature naive B cells in SLE patients produce self-reactive antibodies even before they participate in immune responses as compared with 5–20% in controls. We conclude that SLE is associated with abnormal early B cell tolerance.

Impaired clearance of apoptotic cells in systemic lupus erythematosus: Challenge of T and B cell tolerance

2003 ◽  
Vol 5 (3) ◽  
pp. 175-177 ◽  
Author(s):  
Susanne Kuenkele ◽  
Thomas D. Beyer ◽  
Reinhard E. Voll ◽  
Joachim R. Kalden ◽  
Martin Herrmann
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Apoptotic Cells ◽  
Cell Tolerance ◽  
Systemic Lupus ◽  
B Cell Tolerance

scholarly journals Breakdown of B cell tolerance in a mouse model of systemic lupus erythematosus.

1995 ◽  
Vol 181 (3) ◽  
pp. 1157-1167 ◽  
Author(s):  
J H Roark ◽  
C L Kuntz ◽  
K A Nguyen ◽  
A J Caton ◽  
J Erikson
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Mouse Model ◽  
Transgenic Mice ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Tolerance ◽  
Systemic Lupus ◽  
B Cell Tolerance ◽  
Dna Antibodies

Anti-DNA antibodies, specifically those that stain nuclei in a homogenous nuclear (HN) fashion, are diagnostic of systemic lupus erythematosus (SLE) and the MRL-lpr/lpr SLE murine model. We have used a heavy chain transgene that increases the frequency of anti-HN antibodies to address whether their production in SLE is the consequence of a defect in B cell tolerance. Anti-HN B cells were undetectable in nonautoimmune-prone transgenic mice, but in MRL-lpr/lpr transgenic mice their Ig was evident in the sera and they were readily retrievable as hybridomas. We conclude that nonautoimmune animals actively delete anti-HN-specific B cells, and that MRL-lpr/lpr mice are defective in this process possibly because of the lpr defect in the fas gene.

scholarly journals The Naive B Cell Repertoire Predisposes to Antigen-Induced Systemic Lupus Erythematosus

2003 ◽  
Vol 170 (9) ◽  
pp. 4826-4832 ◽  
Author(s):  
Chuansheng Wang ◽  
Magi Khalil ◽  
Jeffrey Ravetch ◽  
Betty Diamond
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Cell Repertoire ◽  
B Cell Repertoire
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