scholarly journals A transgenic model of autoimmune hemolytic anemia.

1992 ◽  
Vol 175 (1) ◽  
pp. 71-79 ◽  
Author(s):  
M Okamoto ◽  
M Murakami ◽  
A Shimizu ◽  
S Ozaki ◽  
T Tsubata ◽  
...  
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
Disease Model ◽  
Single Chain ◽  
Relative Contribution ◽  
Treatment And Prevention ◽  
Self Tolerance ◽  
Genes Encoding ◽  
Individual Mouse ◽  
Double Transgenic Mice

We made double transgenic mice bearing immunoglobulin heavy and light chain genes encoding an autoantibody against the mouse erythrocyte by the cross of C57BL/6 mice carrying the transgene for each chain of the immunoglobulin. Although no obvious disorders were found in the single-chain transgenic mice, severely anemic symptoms were found in some of the double transgenic mice, in which most B cells express, at least on their surface, the autoantibody reactive to self-antigens on the erythrocyte. Individual double-transgenic mice showed a wide variation of phenotypes between severe anemia and no symptoms. Both deletion and anergy of autoreactive B cells were seen in each individual mouse, but their relative contribution to self-tolerance was variable and not directly related to the severity of anemia or the amount of the autoantibody produced. This transgenic system provides a good autoimmune disease model for exploring its onset mechanism, and means of its treatment and prevention.

Self-Tolerance in B-Cells from Different Lines of Lysozyme Double-Transgenic Mice

1989 ◽  
pp. 377-384 ◽  
Author(s):  
A. Basten ◽  
R. A. Brink ◽  
D. Y. Mason ◽  
J. Crosbie ◽  
C. C. Goodnow
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
Self Tolerance ◽  
Double Transgenic Mice

Effect of Plant Compound Curcumin on the Expression of a-Synuclein in Hippocampal Neurons of APPswe/PS1dE9 Double Transgenic Mice

2013 ◽  
Vol 781-784 ◽  
pp. 643-646
Author(s):  
Xiao Lin ◽  
Li Yu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
Disease Model ◽  
Dependent Manner ◽  
Double Transgenic Mice ◽  
Ad Alzheimer’S Disease ◽  
Dose Dependent

In this study, we aim to investigate the effect of curcumin on the expression of a-synuclein in the APPswe/PS1dE9 double transgenic mice. APPswe/PS1dE9 double transgenic mice were used as AD (Alzheimer's disease) model and fed with different concentrations of curcumin every day for 6 months, then immunohistochemistry method were used to detect the expression of a-synuclein in hippocampus of mice. The expression of a-syn in hippocampal neuron was decreased significantly after treated with 0.16g/kg to 1.0g/kg curcumin, the change was apparent in dose-dependent manner (P<0.05). a-synuclein pay an important role in the genesis and development of Alzheimer's disease and decreased level of a-synuclein might contribute to the neuroprotective effect of Curcumin, which may become a new target for the prevention and treatment of Alzheimer's disease.

scholarly journals Autoantigen-Specific B Cell Activation in FAS-Deficient Rheumatoid Factor Immunoglobulin Transgenic Mice

1999 ◽  
Vol 190 (5) ◽  
pp. 639-650 ◽  
Author(s):  
Haowei Wang ◽  
Mark J. Shlomchik
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
Rheumatoid Factor ◽  
Cell Activation ◽  
Fas Ligand ◽  
Systemic Autoimmune Disease ◽  
B Cell Activation ◽  
Autoantibody Production ◽  
Self Tolerance

In systemic autoimmune disease, self-tolerance fails, leading to autoantibody production. A central issue in immunology is to understand the origins of activated self-reactive B cells. We have used immunoglobulin (Ig) transgenic mice to investigate the regulation of autoreactive B cells with specificity for self-IgG2a (the rheumatoid factor [RF] specificity) to understand how normal mice regulate RF autoantibodies and how this fails in autoimmune mice. We previously showed that normal mice do not tolerize the AM14 RF clone, nor do they appear to activate it. Here we show that in Fas-deficient autoimmune mice, the picture is quite different. RF B cells are activated to divide and secrete, but only when the autoantigen is present. Thus, B cells that are ignored rather than anergized in normal mice can be stimulated to produce autoantibody in Fas-deficient mice. This demonstrates a novel developmental step at which intact Fas–Fas ligand signaling is required to regulate B cells in order to prevent autoimmunity. These data also establish the relevance of ignorant self-specific B cells to autoantibody production in disease and prove that in the case of the RF specificity, the nominal autoantigen IgG2a is the driving autoantigen in vivo.

Induction of self-tolerance in T cells but not B cells of transgenic mice expressing little self antigen

Science ◽  
1991 ◽  
Vol 251 (4998) ◽  
pp. 1223-1225 ◽  
Author(s):  
S Adelstein ◽  
H Pritchard-Briscoe ◽  
T. Anderson ◽  
J Crosbie ◽  
G Gammon ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Transgenic Mice ◽  
Self Tolerance ◽  
Self Antigen

scholarly journals Breakdown of Tolerance to a Neo-Self Antigen in Double Transgenic Mice in Which B Cells Present the Antigen

2000 ◽  
Vol 164 (9) ◽  
pp. 4594-4600 ◽  
Author(s):  
Alexander F. de Vos ◽  
Atsuki Fukushima ◽  
Mark C. Lobanoff ◽  
Barbara P. Vistica ◽  
James C. Lai ◽  
...  
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
Double Transgenic Mice ◽  
Self Antigen

scholarly journals B Lymphocytes Producing Demyelinating Autoantibodies: Development and Function in Gene-targeted Transgenic Mice

1998 ◽  
Vol 188 (1) ◽  
pp. 169-180 ◽  
Author(s):  
Tobias Litzenburger ◽  
Reinhard Fässler ◽  
Jan Bauer ◽  
Hans Lassmann ◽  
Christopher Linington ◽  
...  
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
Cell Population ◽  
Plasma Cells ◽  
Autoimmune Encephalitis ◽  
Normal Numbers ◽  
Self Tolerance ◽  
Normal Differentiation ◽  
And Function

We studied the cellular basis of self tolerance of B cells specific for brain autoantigens using transgenic mice engineered to produce high titers of autoantibodies against the myelin oligodendrocyte glycoprotein (MOG), a surface component of central nervous system myelin. We generated “knock-in” mice by replacing the germline JH locus with the rearranged immunoglobulin (Ig) H chain variable (V) gene of a pathogenic MOG-specific monoclonal antibody. In the transgenic mice, conventional B cells reach normal numbers in bone marrow and periphery and express exclusively transgenic H chains, resulting in high titers of MOG-specific serum Igs. Additionally, about one third of transgenic B cells bind MOG, thus demonstrating the absence of active tolerization. Furthermore, peritoneal B-1 lymphocytes are strongly depleted. Upon immunization with MOG, the mature transgenic B cell population undergoes normal differentiation to plasma cells secreting MOG-specific IgG antibodies, during which both Ig isotype switching and somatic mutation occur. In naive transgenic mice, the presence of this substantial autoreactive B cell population is benign, and the mice fail to develop either spontaneous neurological disease or pathological evidence of demyelination. However, the presence of the transgene both accelerates and exacerbates experimental autoimmune encephalitis, irrespective of the identity of the initial autoimmune insult.

scholarly journals Excess CD40L does not rescue anti-DNA B cells from clonal anergy

F1000Research ◽  
2014 ◽  
Vol 2 ◽  
pp. 218
Author(s):  
Mohammad Aslam ◽  
Yusuke Kishi ◽  
Takeshi Tsubata
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
Lupus Erythematosus ◽  
Tolerance Mechanism ◽  
Autoantibody Production ◽  
Transgenic Mouse Line ◽  
Self Tolerance ◽  
Peripheral Lymphoid Tissue ◽  
Necrosis Factor ◽  
Clonal Anergy

CD40L, a member of the tumor necrosis factor (TNF) ligand family, is overexpressed in patients with systemic lupus erythematosus and in lupus mouse models. Previously, we demonstrated that B cells producing pathogenic anti-Sm/RNP antibodies are deleted in the splenic marginal zone (MZ), and that MZ deletion of these self-reactive B cells is reversed by excess CD40L, leading to autoantibody production. To address whether excess CD40L also perturbs clonal anergy, another self-tolerance mechanism of B cells whereby B cells are functionally inactivated and excluded from follicles in the peripheral lymphoid tissue, we crossed CD40L-transgenic mice with the anti-DNA H chain transgenic mouse line 3H9, in which Ig λ1+ anti-DNA B cells are anergized. However, the percentage and localization of Ig λ1+ B cells in CD40L/3H9 double transgenic mice were no different from those in 3H9 mice. This result indicates that excess CD40L does not perturb clonal anergy, including follicular exclusion. Thus, MZ deletion is distinct from clonal anergy, and is more liable to tolerance break.

scholarly journals Excess CD40L does not rescue anti-DNA B cells from clonal anergy

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 218 ◽  
Author(s):  
Mohammad Aslam ◽  
Yusuke Kishi ◽  
Takeshi Tsubata
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
Lupus Erythematosus ◽  
Tolerance Mechanism ◽  
Autoantibody Production ◽  
Transgenic Mouse Line ◽  
Self Tolerance ◽  
Peripheral Lymphoid Tissue ◽  
Necrosis Factor ◽  
Clonal Anergy

CD40L, a member of the tumor necrosis factor (TNF) ligand family, is overexpressed in patients with systemic lupus erythematosus and in lupus mouse models. Previously, we demonstrated that B cells producing pathogenic anti-Sm/RNP antibodies are deleted in the splenic marginal zone (MZ), and that MZ deletion of these self-reactive B cells is reversed by excess CD40L, leading to autoantibody production. To address whether excess CD40L also perturbs clonal anergy, another self-tolerance mechanism of B cells whereby B cells are functionally inactivated and excluded from follicles in the peripheral lymphoid tissue, we crossed CD40L-transgenic mice with the anti-DNA H chain transgenic mouse line 3H9, in which Ig λ1+ anti-DNA B cells are anergized. However, the percentage and localization of Ig λ1+ B cells in CD40L/3H9 double transgenic mice were no different from those in 3H9 mice. This result indicates that excess CD40L does not perturb clonal anergy, including follicular exclusion. Thus, MZ deletion is distinct from clonal anergy, and is more liable to tolerance break.

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