Identification of a common idiotype on myelin oligodendrocyte glycoprotein-specific autoantibodies in chronic relapsing experimental allergic encephalomyelitis

Gunn, Catherine; Suckling, A.J.; Linington, Christopher

doi:10.1016/0165-5728(89)90028-3

Cited by 18 publications

(7 citation statements)

References 14 publications

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“…3, A and C ). Using rabbit antiidiotypic Abs recognizing specifically the V region of the H chain of 8.18-C5 (24), we confirmed that the overwhelming majority of transgenic B cells indeed express the 8.18-C5 V H idiotype (Fig. 3 A ).…”

Section: Resultssupporting

confidence: 54%

“…Red blood cells were lysed by incubation in 0.165 M NH 4 Cl for 10 min. Cells were washed with PBS/1% FCS and stained with the following Ab conjugates: anti–IgM a -FITC (clone DS-1; PharMingen, San Diego, CA); anti–IgM b -BIOTIN (clone AF6-78; PharMingen); anti–CD43-FITC (clone S7; PharMingen); anti–B220-PE (PharMingen); anti–CD5-FITC (clone 53-7.3; PharMingen); anti-IgD (Nordic Immunology Labs, Tilburg, The Netherlands); and 8.18-C5 idiotype–specific Ab (24). Biotinamidocaproate- N -hydroxysuccinimide ester (Sigma Chemical Co., Munich, Germany) was used for biotin labeling of recombinant truncated rat MOG (25), which was applied in a 1:500 dilution for staining.…”

Section: Methodsmentioning

confidence: 99%

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

Litzenburger

Fässler

Bauer

et al. 1998

The Journal of Experimental Medicine

233

213

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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.

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Section: Resultssupporting

confidence: 54%

Section: Methodsmentioning

confidence: 99%

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

Litzenburger

Fässler

Bauer

et al. 1998

The Journal of Experimental Medicine

233

213

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“…RR mice, both single and double transgenic, produce MOG-specific autoantibodies that share their dominant isotype, IgG1, with the original demyelinating anti-MOG mAb 8.18-C5 and that, in vivo, aggravate EAE when transferred i.v. (27). Importantly, we found large Ig deposits in the demyelinating lesions of single- and double-transgenic RR mice.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous relapsing-remitting EAE in the SJL/J mouse: MOG-reactive transgenic T cells recruit endogenous MOG-specific B cells

Pöllinger

Krishnamoorthy

Berer

et al. 2009

Journal of Experimental Medicine

257

222

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We describe new T cell receptor (TCR) transgenic mice (relapsing-remitting [RR] mice) carrying a TCR specific for myelin oligodendrocyte glycoprotein (MOG) peptide 92–106 in the context of I-As. Backcrossed to the SJL/J background, most RR mice spontaneously develop RR experimental autoimmune encephalomyelitis (EAE) with episodes often altering between different central nervous system tissues like the cerebellum, optic nerve, and spinal cord. Development of spontaneous EAE depends on the presence of an intact B cell compartment and on the expression of MOG autoantigen. There is no spontaneous EAE development in B cell–depleted mice or in transgenic mice lacking MOG. Transgenic T cells seem to expand MOG autoreactive B cells from the endogenous repertoire. The expanded autoreactive B cells produce autoantibodies binding to a conformational epitope on the native MOG protein while ignoring the T cell target peptide. The secreted autoantibodies are pathogenic, enhancing demyelinating EAE episodes. RR mice constitute the first spontaneous animal model for the most common form of multiple sclerosis (MS), RR MS.

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“…Single cell suspensions were prepared from spleen, LNs, peritoneal cells, and bone marrow from 6-8-wk-old mice and processed. Red blood cells were lysed by incubation in 0.165 M NH 4 (24). Biotinamidocaproate-N -hydroxysuccinimide ester (Sigma Chemical Co., Munich, Germany) was used for biotin labeling of recombinant truncated rat MOG (25), which was applied in a 1:500 dilution for staining.…”

Section: Methodsmentioning

confidence: 99%

B lymphocytes producing demyelinating autoantibodies: Development and function in gene-targeted transgenic mice

Litzenburger

Fässler²,

Bauer³

et al. 1998

Journal of Neuroimmunology

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Identification of a common idiotype on myelin oligodendrocyte glycoprotein-specific autoantibodies in chronic relapsing experimental allergic encephalomyelitis

Cited by 18 publications

References 14 publications

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

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

Spontaneous relapsing-remitting EAE in the SJL/J mouse: MOG-reactive transgenic T cells recruit endogenous MOG-specific B cells

B lymphocytes producing demyelinating autoantibodies: Development and function in gene-targeted transgenic mice

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