B cells and autoantibodies: complex roles in CNS injury

Ankeny, Daniel P.; Popovich, Phillip G.

doi:10.1016/j.it.2010.06.006

Cited by 91 publications

(63 citation statements)

References 60 publications

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“…Despite these limitations, we offer evidence that after SCI, peripheral blood mononuclear cells overexpress BCMA, BAFF, and APRIL. Based on previous studies, 7,22,29 we speculate that this promotes SCI-induced autoimmunity by allowing B cells to become activated by CNS debris and escape clonal deletion. These activated B cells secrete autoantibodies that contribute to tissue damage and neurotoxicity after SCI.…”

Section: Discussionmentioning

confidence: 69%

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B-Cell Maturation Antigen, A Proliferation-Inducing Ligand, and B-Cell Activating Factor Are Candidate Mediators of Spinal Cord Injury-Induced Autoimmunity

Saltzman¹,

Battaglino

Salles

et al. 2013

Journal of Neurotrauma

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Autoimmunity is thought to contribute to poor neurological outcomes after spinal cord injury (SCI). There are few mechanism-based therapies, however, designed to reduce tissue damage and neurotoxicity after SCI because the molecular and cellular bases for SCI-induced autoimmunity are not completely understood. Recent groundbreaking studies in rodents indicate that B cells are responsible for SCI-induced autoimmunity. This novel paradigm, if confirmed in humans, could aid in the design of neuroprotective immunotherapies. The aim of this study was to investigate the molecular signaling pathways and mechanisms by which autoimmunity is induced after SCI, with the goal of identifying potential targets in therapies designed to reduce tissue damage and inflammation in the chronic phase of SCI. To that end, we performed an exploratory microarray analysis of peripheral blood mononuclear cells to identify differentially expressed genes in chronic SCI. We identified a gene network associated with lymphoid tissue structure and development that was composed of 29 distinct molecules and five protein complexes, including two cytokines, a proliferation-inducing ligand (APRIL) and B-cell-activating factor (BAFF), and one receptor, B-cell maturation antigen (BMCA) involved in B cell development, proliferation, activation, and survival. Real-time polymerase chain reaction analysis from ribonucleic acid samples confirmed upregulation of these three genes in SCI. To our knowledge, this is the first report that peripheral blood mononuclear cells produce increased levels of BAFF and APRIL in chronic SCI. This finding provides evidence of systemic regulation of SCI-autoimmunity via APRIL and BAFF mediated activation of B cells through BMCA and points toward these molecules as potential targets of therapies designed to reduce neuroinflammation after SCI.

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Section: Discussionmentioning

confidence: 69%

“…7,18,19 For instance, animal models of multiple sclerosis have demonstrated natural IgM autoantibodies that play a protective role enhancing remyelination and preventing neuronal apoptosis. 20,21 Similarly, mice deficient in mature B cells demonstrated greater neuron survival after intravitreal glutamate injections.…”

Section: Discussionmentioning

confidence: 99%

B-Cell Maturation Antigen, A Proliferation-Inducing Ligand, and B-Cell Activating Factor Are Candidate Mediators of Spinal Cord Injury-Induced Autoimmunity

Saltzman¹,

Battaglino

Salles

et al. 2013

Journal of Neurotrauma

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“…It is suggested that increased cytokine production at the injury site is correlated with the augmentation of neural injury [16]. However, production of autoantibodies and activation of numerous inflammatory pathways causes activated B-cell accumulation at the SCI region, correlated with the pathological events after SCI [17].…”

Section: Introductionmentioning

confidence: 99%

B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury

et al. 2016

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Spinal cord injury (SCI) is a highly debilitating pathology that has irreversible impacts and results in functional loss. We evaluated the anti-inflammatory and immunologic role of antibody-mediated depletion of B cells through the glycoengineered anti-muCD20 antibody (18B12) in an experimental model of spinal cord compression, in vivo and ex vivo. Intraperitoneal 18B12 was administered at a dose of 30 mg/kg, 1 h and 6 h after SCI, and mice were sacrificed 24 h after trauma. We demonstrated, in vivo, that 18B12 slowed severe hindlimb motor dysfunction (Basso Mouse Scale score) and neuronal death by histological evaluation in SCI mice, as well as decreased expression of nuclear factor-kB, inducible nitric oxide synthase, cytokines, and glial fibrillary acidic protein. Also, 18B12 reduced expression of microglia, just as it lowered the expression of B and T lymphocytes. Moreover, in spinal cord organotypic cultures, pretreatment with 18B12 significantly reduced nitric oxide expression and protected cells from cell death [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay]. In this study, we showed that 18B12 treatment reduces the development of inflammation and tissue injury by alteration of the immune system associated with SCI. This study increases the current knowledge that B-cell depletion is able to exert immunomodulating actions in damaged spinal cords.

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“…In recent year's the knowledge about the alterations occurred after Traumatic Brain Injury (TBI) has undergone significant developments [1]. These advances have contributed to clarify the relationship between post-traumatic edema and neuropathological sequelae that are largely responsible for involvement of this protein in apoptosis, tumors development, angiogenesis, cell invasion [10][11][12], and also altered gene expression patterns of hnRNPK have been found in many human cancers [13,14].…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous Nuclear Ribonucleoprotein K Autoantibodies in Patients who Suffered Severe Traumatic Brain Injury

Acevedo-Calado¹,

Montes-Cano

Murillo-Cabezas³

et al. 2014

SOJI

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B cells and autoantibodies: complex roles in CNS injury

Cited by 91 publications

References 60 publications

B-Cell Maturation Antigen, A Proliferation-Inducing Ligand, and B-Cell Activating Factor Are Candidate Mediators of Spinal Cord Injury-Induced Autoimmunity

B-Cell Maturation Antigen, A Proliferation-Inducing Ligand, and B-Cell Activating Factor Are Candidate Mediators of Spinal Cord Injury-Induced Autoimmunity

B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury

Heterogeneous Nuclear Ribonucleoprotein K Autoantibodies in Patients who Suffered Severe Traumatic Brain Injury

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