Reassessing B cell contributions in multiple sclerosis

  title={Reassessing B cell contributions in multiple sclerosis},
  author={Rui Li and Kristina R. Patterson and Amit Bar-Or},
  journal={Nature Immunology},
There is growing recognition that B cell contributions to normal immune responses extend well beyond their potential to become antibody-producing cells, including roles at the innate–adaptive interface and their potential to modulate the responses of other immune cells such as T cells and myeloid cells. These B cell functions can have both pathogenic and protective effects in the context of central nervous system (CNS) inflammation. Here, we review recent advances in the field of multiple… 
Role of B cells and antibodies in multiple sclerosis.
Therapies for multiple sclerosis targeting B cells
  • R. Milo
  • Biology
    Croatian medical journal
  • 2019
Ocrelizumab is the first disease-modifying drug that has shown efficacy in primary-progressive MS, and is currently approved for both indications and another promising approach is the inhibition of Bruton's tyrosine kinase, a key enzyme that mediates B cell activation and survival, by agents such as evobrutinib.
Learning from other autoimmunities to understand targeting of B cells to control multiple sclerosis.
AMemory B cell centric mechanism can integrate: potential aetiology, genetics, pathology and response to therapy in multiple sclerosis and other autoimmune conditions with ectopic B cell activation that are responsive to memory B cell-depleting strategies.
B cells in central nervous system disease: diversity, locations and pathophysiology
Overall, understanding common and divergent principles of B cell accumulation and their effects within the CNS could offer new insights into treating these devastating neurological conditions.
Relevance of Pathogenetic Mechanisms to Clinical Effectiveness of B-Cell-Depleting Monoclonal Antibodies in Multiple Sclerosis
The immunopathogenesis of MS is summarised with a focus on onset of autoimmunity and compartmentalisation of the immune response; mechanisms mediating B-cell depletion and underlying the effectiveness of B- cell-depleting mAbs are also discussed.
The CD8 T Cell-Epstein-Barr Virus-B Cell Trialogue: A Central Issue in Multiple Sclerosis Pathogenesis
The results of human studies that have contributed to elucidate the role of CD8 T cells in MS immunopathogenesis are reviewed, and current understanding of autoreactivity, B-cell and EBV involvement in MS, and mechanism of action of different MS treatments are discussed.
When a T cell engages a B cell: novel insights in multiple sclerosis.
Important new insights are summarized into the interaction between these two cell populations and recent observations regarding how memory B cells activate brain-homing autoreactive T cells in multiple sclerosis are outlined.
Novel contributors to B cell activation during inflammatory CNS demyelination; An oNGOing process
Current evidence for BAFF-dependent signaling through the NgR multimeric complex is provided, elucidating their association within the CNS compartment and underlying the importance of these potential pathogenic molecular regulators as possible therapeutic targets to limit relapse rates and potentially MS progression.


The Ins and Outs of B Cells in Multiple Sclerosis
This review will assess the current knowledge of the mechanisms and pathways governing B cell migration into the CNS and examine evidence for and against a compartmentalized B cell response driving progressive MS pathology.
B Cells in the Multiple Sclerosis Central Nervous System: Trafficking and Contribution to CNS-Compartmentalized Inflammation
Characteristics of human B cells identified within distinct CNS subcompartments of patients with MS, including the cerebrospinal fluid, parenchymal lesions, and meninges are reviewed, as well as the relationship between B cell populations identified in these sub compartments and the periphery.
B cells and antibodies in multiple sclerosis pathogenesis and therapy
Key features of B-cell biology, the role of B cells and antibodies in CNS inflammation, and current attempts to identify the targets of pathogenic antibodies in MS are summarized.
Cytokine-Defined B Cell Responses as Therapeutic Targets in Multiple Sclerosis
Important antibody-independent pathogenic roles of B cells are emerging in autoimmune diseases, including multiple sclerosis (MS). The contrasting results of different treatments targeting B cells in
Effector T Cells in Multiple Sclerosis.
Although the majority of research on MS pathogenesis has centered on the role of effector CD4 T cells, accumulating data suggests that CD8 T cells may play a significant role in the human disease.
B cell exchange across the blood-brain barrier in multiple sclerosis.
Deep repertoire sequencing of IgG heavy chain variable region genes in paired cerebrospinal fluid and PB samples from patients with MS and other neurological diseases found that a restricted pool of clonally related B cells participated in robust bidirectional exchange across the BBB, suggesting that CNS-directed autoimmunity may be triggered and supported on both sides of theBBB.
Specific peripheral B cell tolerance defects in patients with multiple sclerosis.
It is demonstrated that in contrast to patients with RA or T1D, bone marrow central B cell selection in MS appears normal in most patients, and patients with MS suffer from a specific peripheral B cell tolerance defect that is potentially attributable to impaired Treg function and that leads to the accumulation of autoreactive B cell clones in their blood.
Effect of Natalizumab on Circulating CD4+ T-Cells in Multiple Sclerosis
Natalizumab treatment selectively increased the effector memory T-cell pool but not the activation state of T-cells in the blood compartment and myelin-reactive T- cells in particular showed signs of increased immune activation.
Antibody-independent functions of B cells: a focus on cytokines
B cells can regulate inflammatory immune responses, primarily through their provision of IL-10 and IL-35, and the rational for targeting these cells in the clinic is discussed.
B cells regulate autoimmunity by provision of IL-10
Data show that B cell–derived IL-10 plays a key role in controlling autoimmunity and that recovery was dependent on the presence of autoantigen-reactive B cells.