B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide

Lyons, Joseph; San, Manuel; Happ, Mary Pat; Cross, Anne H.

doi:10.1002/(sici)1521-4141(199911)29:11<3432::aid-immu3432>3.0.co;2-2

Cited by 263 publications

(194 citation statements)

References 33 publications

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“…(Lyons et al, 1999(Lyons et al, , 2002Sekiguchi et al, 2009), other studies suggest that the humoral response elicited by active immunization with MOG 35-55 could contribute to EAE pathogenesis. Some data indeed indicate that B cell depletion during MOG 35-55 -induced EAE progression suppressed EAE symptoms, a clinical benefit which was associated with reduction of anti-MOG peptide antibody titers (Matsushita et al, 2008).…”

Section: Discussionmentioning

confidence: 96%

Antibody response in MOG35–55 induced EAE

Lalive

Molnarfi

Benkhoucha

et al. 2011

Journal of Neuroimmunology

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Neurological deficit in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis is widely considered to be a consequence of synergistic T and B cell responses to central nervous system (CNS) antigens. We show that mice immunized with encephalitogenic myelin oligodendrocyte glycoprotein ) peptide develop significant serum levels of anti-MOG antibodies in parallel with disease progression. Furthermore, EAE mice developed antibodies against DNA and RNA, a serological hallmark observed in autoimmune diseases such as systemic lupus erythematosus. The presence of anti-nucleic responsive B cells and antibodies during EAE may highlight a previously unappreciated mechanism in the pathogenesis of CNS autoimmunity.

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Section: Discussionmentioning

confidence: 96%

Antibody response in MOG35–55 induced EAE

Lalive

Molnarfi

Benkhoucha

et al. 2011

Journal of Neuroimmunology

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“…This boost may have obscured the regulatory role of TLR4 and TLR9 that is clearly seen with a more traditional induction procedure. The use of MOG protein rather than MOG peptide may also be the reason for the observed differences, because in contrast to MOG peptide, immunization with MOG protein induces pathogenic B cell responses and demyelinating antibodies similar to human MS [40,41]. Furthermore, CD8 T cell responses are elicited after MOG protein immunization.…”

Section: Discussionmentioning

confidence: 99%

Unexpected regulatory roles of TLR4 and TLR9 in experimental autoimmune encephalomyelitis

et al. 2008

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Innate immune mechanisms essential for priming encephalitogenic T cells in autoimmune neuroinflammation are poorly understood. Experimental autoimmune encephalomyelitis (EAE) is a IL-17-producing Th (Th17) cell-mediated autoimmune disease and an animal model of multiple sclerosis. To investigate how upstream TLR signals influence autoimmune T cell responses, we studied the role of individual TLR and MyD88, the common TLR adaptor molecule, in the initiation of innate and adaptive immune responses in EAE. Wild type (WT) C57BL/6, TLR-deficient and MyD88-deficient mice were immunized with myelin oligodendrocyte glycoprotein (MOG) in CFA. MyD88 -/-mice were completely EAE resistant. Purified splenic myeloid DC (mDC) from MyD88 -/-mice expressed much less IL-6 and IL-23, and serum and T cell IL-17 were absent. TLR4-/-and TLR9 -/-mice surprisingly exhibited more severe EAE symptoms than WT mice. IL-6 and IL-23 expression by mDC and Th17 responses were higher in TLR4 -/-mice, suggesting a regulatory role of TLR4 in priming Th17 cells. IL-6 expression by splenocytes was higher in TLR9 -/-mice. Our data suggest that MyD88 mediates the induction of mDC IL-6 and IL-23 responses after MOG immunization, which in turn drives IL-17-producing encephalitogenic Th17 cell activation. Importantly, we demonstrate that TLR4 and TLR9 regulate disease severity in MOGinduced EAE.

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“…The formation of these ectopic follicles indicates that B cells migrate to the brain, are activated locally and present antigens, and differentiate into memory B cells or plasmablasts within the CNS, rather than being activated in the periphery and homing to the CNS in a fully mature state. The establishment of germinal centers in the brain may reflect differences in the immune response in RRMS and SPMS (Lyons et al, 1999;Magliozzi et al, 2007). …”

Section: B Cells As Antigen Presenting Cellsmentioning

confidence: 99%

Chapter 4 B Cells and Autoantibodies in the Pathogenesis of Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

McLaughlin

Wucherpfennig

2008

Advances in Immunology

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The mainstream view is that MS is caused by an autoimmune attack of the CNS myelin by myelin-specific CD4 T cells, and this perspective is supported by extensive work in the experimental autoimmune encephalomyelitis (EAE) model of MS as well as immunological and genetic studies in humans. However, it is important to keep in mind that other cell populations of the immune system are also essential in the complex series of events leading to MS, as exemplified by the profound clinical efficacy of B cell depletion with Rituximab. This review discusses the mechanisms by which B cells contribute to the pathogenesis of MS and dissects their role as antigen-presenting cells (APCs) to T cells with matching antigen specificity, the production of proinflammatory cytokines and chemokines, as well as the secretion of autoantibodies that target structures on the myelin sheath and the axon. Mechanistic dissection of the interplay between T cells and B cells in MS may permit the development of B cell based therapies that do not require depletion of this important cell population.

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B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide

Cited by 263 publications

References 33 publications

Antibody response in MOG35–55 induced EAE

Antibody response in MOG35–55 induced EAE

Unexpected regulatory roles of TLR4 and TLR9 in experimental autoimmune encephalomyelitis

Chapter 4 B Cells and Autoantibodies in the Pathogenesis of Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

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