B cell recognition of myelin oligodendrocyte glycoprotein autoantigen depends on immunization with protein rather than short peptide, while B cell invasion of the CNS in autoimmunity does not

Dang, Amy K.; Jain, Rajiv W.; Craig, Heather C; Kerfoot, Steven M.

doi:10.1016/j.jneuroim.2014.12.008

Cited by 25 publications

(59 citation statements)

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“…Distinct B cell subtypes have recently been associated with EAE disease progression and regulation (6, 7, 16, 53, 56-59), and are at least partially dependent on the choice of antigen (protein or peptide) used to induce the disease (18). A role for B cells has also been suggested in different models of recombinant MOG (rMOG)-induced EAE (18, 60-62). In general, when rMOG was used to induce EAE, pathogenic B cells were induced, and their depletion resulted in less EAE severity (18, 60-62).…”

Section: Discussionmentioning

confidence: 99%

“…A role for B cells has also been suggested in different models of recombinant MOG (rMOG)-induced EAE (18, 60-62). In general, when rMOG was used to induce EAE, pathogenic B cells were induced, and their depletion resulted in less EAE severity (18, 60-62). However, even these studies varied in the type of rMOG used, e.g., human (18) versus mouse (60-62).…”

Section: Discussionmentioning

confidence: 99%

“…In general, when rMOG was used to induce EAE, pathogenic B cells were induced, and their depletion resulted in less EAE severity (18, 60-62). However, even these studies varied in the type of rMOG used, e.g., human (18) versus mouse (60-62). Whether a greater mobilization of Bregs can be achieved using MOG-pσ1 in rMOG-induced EAE, remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Abs induced to different MOG peptides as a result of epitope spreading (64) or immunization with MOG protein do contribute to EAE pathogenicity (60-63, 65). Such evidence is consistent with the notion that Abs to the MOG protein are pathogenic to MS patients (66, 67).…”

Section: Discussionmentioning

confidence: 99%

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Regulatory T Cell Dysfunction Acquiesces to BTLA+ Regulatory B Cells Subsequent to Oral Intervention in Experimental Autoimmune Encephalomyelitis

Huarte

Jun

Rynda‐Apple

et al. 2016

The Journal of Immunology

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Regulatory T cells (Tregs) induced during autoimmunity often become quiescent and unable to resolve disease, suggesting inadequate activation. Resolution of established experimental autoimmune encephalomyelitis (EAE) can be achieved with myelin oligodendrocyte glycoprotein (MOG) fused to reovirus protein σ1 (MOG-pσ1) which activates Tregs, restoring protection, but requiring other regulatory cells to revitalize them. B cells have a dichotomous role in both the pathogenesis and recovery from EAE. While inflammatory B cells contribute to EAE’s pathogenesis, treatment of EAE mice with MOG-pσ1, but not OVA-pσ1, resulted in an influx of IL-10-producing B220+CD5+ B regulatory cells (Bregs) enabling Tregs to recover their inhibitory activity, and in turn, leading to the rapid amelioration of EAE. These findings implicate direct interactions between Bregs and Tregs to facilitate this recovery. Adoptive transfer of B220+CD5− B cells from MOG-pσ1-treated EAE or Bregs from PBS-treated EAE mice did not resolve disease while the adoptive transfer of MOG-pσ1-induced B220+CD5+ Bregs greatly ameliorated EAE. MOG-pσ1-, but not OVA-pσ1-induced IL-10-producing Bregs, expressed elevated levels of BTLA relative to CD5− B cells, as opposed to Tregs or effector T (Teff) cells, whose BTLA expression was not affected. These induced Bregs restored EAE Treg function in a BTLA-dependent manner. BTLA−/− mice showed more pronounced EAE with fewer Tregs but, upon adoptive transfer of MOG-pσ1-induced BTLA+ Bregs, BTLA−/− mice were protected against EAE. Hence, this evidence shows the importance of BTLA in activating Tregs to facilitate recovery from EAE.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Regulatory T Cell Dysfunction Acquiesces to BTLA+ Regulatory B Cells Subsequent to Oral Intervention in Experimental Autoimmune Encephalomyelitis

Huarte

Jun

Rynda‐Apple

et al. 2016

The Journal of Immunology

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“…These mice express a knock-in transgenic IgH chain derived from a MOG-specific antibody; thus, around 30% of their B cells are therefore specific for MOG protein [14]. IgH[MOG] animals develop severe EAE when immunized with either whole MOG protein [14] or with its extracellular domain (MOG [1-125] )[15], indicating an important role for MOG-reactive B cells in neuroimmune processes. However the potential mechanisms by which MOG-reactive B cells facilitate T cell-driven pathogenicity, such as in class II-restricted peptide immunization models of EAE, remain incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

Myelin-reactive B cells exacerbate the severity of CD4⁺T cell-driven CNS autoimmunity in an IL-23-dependent manner

Yeola

Mailhot

Baillargeon

et al. 2019

Preprint

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1 8 BACKGROUND: Multiple sclerosis (MS) is an autoimmune disorder of the central 1 9 3 1 cells was studied by flow cytometry. The capacity of IgH[MOG] B cells to present 3 2 antigen to CD4 + T cells was assessed using in vitro priming assays with MOG [35-3 3 55] as the antigen.3 4 3 5 RESULTS: MOG [35-55] -immunized IgH[MOG] mice rapidly developed severe EAE 3 6 characterized by leukocytic infiltration and demyelination in the brain, spinal cord 3 7 and optic nerve. Notably, while the frequency of CD4 + T cells was increased in 3 8 the CNS of IgH[MOG] with severe disease relative to controls, no differences 3 9 were observed with respect to the frequency of B cells. Further, IgH[MOG] CNS-4 0 3 infiltrating CD4 + T cells produced significantly higher levels of Th17-associated 4 1 cytokines GM-CSF and IL-17 compared to those from controls. Mechanistically, 4 2 IgH[MOG] B cells were better able than WT B cells to elicit inflammatory cytokine 4 3production from MOG -specific CD4 + T cells in in vitro priming assays. 4 4 4 5 CONCLUSION: These data show that MOG-specific B cells contribute to CD4 + T 4 6 cell-driven EAE by promoting CD4 + T cell inflammation and recruitment to the 4 7 CNS. 4 8 4 9

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B cells in multiple sclerosis

Wang,

Gommerman

2024

Mechanisms of Disease Pathogenesis in Multiple Sclerosis

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B cell recognition of myelin oligodendrocyte glycoprotein autoantigen depends on immunization with protein rather than short peptide, while B cell invasion of the CNS in autoimmunity does not

Cited by 25 publications

References 46 publications

Regulatory T Cell Dysfunction Acquiesces to BTLA+ Regulatory B Cells Subsequent to Oral Intervention in Experimental Autoimmune Encephalomyelitis

Regulatory T Cell Dysfunction Acquiesces to BTLA+ Regulatory B Cells Subsequent to Oral Intervention in Experimental Autoimmune Encephalomyelitis

Myelin-reactive B cells exacerbate the severity of CD4⁺T cell-driven CNS autoimmunity in an IL-23-dependent manner

B cells in multiple sclerosis

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B cell recognition of myelin oligodendrocyte glycoprotein autoantigen depends on immunization with protein rather than short peptide, while B cell invasion of the CNS in autoimmunity does not

Cited by 25 publications

References 46 publications

Regulatory T Cell Dysfunction Acquiesces to BTLA+ Regulatory B Cells Subsequent to Oral Intervention in Experimental Autoimmune Encephalomyelitis

Regulatory T Cell Dysfunction Acquiesces to BTLA+ Regulatory B Cells Subsequent to Oral Intervention in Experimental Autoimmune Encephalomyelitis

Myelin-reactive B cells exacerbate the severity of CD4+T cell-driven CNS autoimmunity in an IL-23-dependent manner

B cells in multiple sclerosis

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Myelin-reactive B cells exacerbate the severity of CD4⁺T cell-driven CNS autoimmunity in an IL-23-dependent manner