Oligodendrocyte-reactive O1, O4, and HNK-1 monoclonal antibodies are encoded by germline immunoglobulin genes

Asakura, Koichi; Miller, David J.; Pogulis, Robert J.; Pease, Larry R.; Rodriguez, Moses

doi:10.1016/0169-328x(95)00190-4

Cited by 22 publications

(24 citation statements)

References 34 publications

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“…The Figure 6 shows the VH gene derived from the frequently expressed VHJ558 family, with only three replacement mutations. If the germline gene corresponding to the V gene of CO17 -1A is unknown, this V sequence is identical with the sequences reported for natural autoantibodies O1, O4, and E7, 42 providing strong evidence that the CO17 -1A V segment is directly encoded by a germline V gene. The 1083 -17 -1A hybridoma was found to elicit tumors in 100% of naive animals when s.c. injected (20Â10 6 cells to three groups of 10 immunized mice and one group of 10 unimmunized mice).…”

Section: Cd4 But Not Cd8 T Cells Are Critical For Tumor Protectionsupporting

confidence: 68%

Recombinant vaccinia viruses expressing immunoglobulin variable regions efficiently and selectively protect mice against tumoral B-cell growth

et al. 2001

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The variable regions of the immunoglobulin ( Ig ) expressed on the surface of a malignant B cell can be considered tumor -specific antigens and, as such, could be targets for immunotherapeutic approaches. However, because until now the immunization procedures have been complex and have given only partial protection, it was necessary to find new methods of immunotherapy.Here, we present a successful method of vaccination against B -cell tumors in a murine model. We produced recombinant vaccinia viruses ( rVV ) expressing the heavy and the light chain of surface Ig of a patient's malignant B cells and we tested the ability of these rVV to protect immunized mice against tumor growth of transfectomas producing the same human Ig. The protection of the mice was complete and specific to the variable region of the immunizing heavy chain although specific lymphoproliferative and cytotoxic responses were not detectable in vitro. The protection was strictly dependent on the presence of CD4 T cells and asialo GM1 + cells. Furthermore, tumor protection clearly required -interferon and was partially inhibited by blocking the Fas -Fas ligand interaction. We also show, in a murine syngeneic model, that rVV expressing a poorly mutated Ig protects against the growth of Ig -producing tumor. Cancer Gene Therapy ( 2001 ) 8, 815 -826

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Section: Cd4 But Not Cd8 T Cells Are Critical For Tumor Protectionsupporting

confidence: 68%

Recombinant vaccinia viruses expressing immunoglobulin variable regions efficiently and selectively protect mice against tumoral B-cell growth

et al. 2001

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“…16 They all had relatively conserved germline sequences. 17,18 Based on this observation, we asked whether natural autoantibodies could be present in the human population. We sought patients with disease processes that cause them to make their own mAbs, specifically patients with multiple myeloma, Waldenstrom syndrome, and monoclonal gammopathy of unknown significance.…”

Section: Role Of Autoantibodies In the Promotionmentioning

confidence: 99%

Invited Article: Human natural autoantibodies in the treatment of neurologic disease

Rodriguez

Warrington

Pease³

2009

Neurology

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Naturally occurring autoantibodies are molecules that are part of the normal immunoglobulin repertoire. This review focuses on three distinct groups of human monoclonal antibodies (mAb). These are human natural autoantibodies that, when injected into an animal model of human disease, stimulate remyelination in CNS demyelinating diseases, protect neurons and extend neuronal processes in CNS axonal disorders, and activate immune dendritic cells to produce cytotoxic T cells to clear metastatic tumors. Natural autoantibodies react to self antigens and are of relatively low affinity. They are derived from germline immunoglobulin genes and are usually polyreactive. Our experiments demonstrated CNS entry by autoradiography of labeled mAb and by MRI. Remyelinating mAb rHIgM22 clusters beta-integrin and mouse mAb O4 recognizes sulfatide. Neuronal outgrowth mAbs sHIgM42 and sHIgM12 appear to target carbohydrates on the surface of neurons. The mAb sHIgM12 (B7-DC-Xab) also is promising as therapeutic against metastatic tumors. It functions by binding and cross-linking the antigen B7-DC on dendritic cells, inducing tumor-specific cytotoxic T cells. All these mAbs activate a transient increase in intracellular calcium, signal via NFkappab, and prevent apoptosis. The mAbs engage downstream signaling events that induce the primary function of the cell (that is, remyelination for oligodendrocytes, axonal preservation and neurite extension for neurons, or antigen presentation for dendritic cells). Natural human auto mAbs are a potentially important therapeutic technique in combating a wide spectrum of disease processes.

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“…Recently, several autoantibodies of the IgM isotype, including a few oligodendrocytereactive antibodies, have been demonstrated to promote remyelination in the Theiler's murine encephalomyelitis virus-induced model for MS (Asakura et al, 1998;Miller et al, 1994;Miller and Rodriguez, 1995). These antibodies promoting remyelination also have the characteristics of "natural autoantibodies" (Asakura et al, 1995;Asakura et al, 1998;Warrington et al, 2000). Natural autoantibodies are mostly of the IgM isotype, have polyreactivity toward multiple self and nonself antigens and are encoded by germline Ig genes with little or no mutations (Asakura et al, 1995;Kirschning et al, 1999;Miller and Rodriguez, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…These antibodies promoting remyelination also have the characteristics of "natural autoantibodies" (Asakura et al, 1995;Asakura et al, 1998;Warrington et al, 2000). Natural autoantibodies are mostly of the IgM isotype, have polyreactivity toward multiple self and nonself antigens and are encoded by germline Ig genes with little or no mutations (Asakura et al, 1995;Kirschning et al, 1999;Miller and Rodriguez, 1995).…”

Section: Introductionmentioning

confidence: 99%

Polyreactive myelin oligodendrocyte glycoprotein antibodies: Implications for systemic autoimmunity in progressive experimental autoimmune encephalomyelitis

Peterson

Tsunoda

Masaki

et al. 2007

Journal of Neuroimmunology

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Two myelin oligodendrocyte glycoprotein ) monoclonal antibodies (mAbs) were produced from an A.SW mouse with progressive experimental autoimmune encephalomyelitis. Polyreactivity/specificity of the mAbs was demonstrated by ELISA. Functionality and a potential role in pathogenesis of systemic autoimmunity were demonstrated in vitro in a lymphocytotoxicity assay and in vivo upon injection into naïve mice. Injection of MOG mAb producing hybridomas into naïve mice resulted in immunoglobulin deposition in kidneys and liver. This model will be useful in determining whether transitional forms between CNS (organ)-specific and systemic autoimmune diseases exist, and whether progressive multiple sclerosis has features of a systemic autoimmune disease.

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Oligodendrocyte-reactive O1, O4, and HNK-1 monoclonal antibodies are encoded by germline immunoglobulin genes

Cited by 22 publications

References 34 publications

Recombinant vaccinia viruses expressing immunoglobulin variable regions efficiently and selectively protect mice against tumoral B-cell growth

Recombinant vaccinia viruses expressing immunoglobulin variable regions efficiently and selectively protect mice against tumoral B-cell growth

Invited Article: Human natural autoantibodies in the treatment of neurologic disease

Polyreactive myelin oligodendrocyte glycoprotein antibodies: Implications for systemic autoimmunity in progressive experimental autoimmune encephalomyelitis

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