B cells and antibodies in CNS demyelinating disease

Cross, Anne H.; Trotter, John L.; Lyons, Joseph

doi:10.1016/s0165-5728(00)00409-4

Cited by 215 publications

(137 citation statements)

References 133 publications

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“…Effector cytokine functions and other Ab-independent roles of B cells are of increasing interest in MS (38), as chronically activated B cells have been described within the meninges of patients with an apparent recapitulation of GC-like architecture (39 -42). Such ectopic lymph node structures have been described in the target organs of several other human autoimmune diseases, including Sjogren's syndrome, diabetes, gastritis, and rheumatoid arthritis (43)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Distinct Effector Cytokine Profiles of Memory and Naive Human B Cell Subsets and Implication in Multiple Sclerosis

Duddy

Niino

Adatia

et al. 2007

The Journal of Immunology

584

594

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Although recent animal studies have fuelled growing interest in Ab-independent functions of B cells, relatively little is known about how human B cells and their subsets may contribute to the regulation of immune responses in either health or disease. In this study, we first confirm that effector cytokine production by normal human B cells is context dependent and demonstrate that this involves the reciprocal regulation of proinflammatory and anti-inflammatory cytokines. We further report that this cytokine network is dysregulated in patients with the autoimmune disease multiple sclerosis, whose B cells exhibit a decreased average production of the down-regulatory cytokine IL-10. Treatment with the approved chemotherapeutic agent mitoxantrone reciprocally modulated B cell proinflammatory and anti-inflammatory cytokines, establishing that the B cell cytokine network can be targeted in vivo. Prospective studies of human B cells reconstituting following in vivo depletion suggested that different B cell subsets produced distinct effector cytokines. We confirmed in normal human B cell subsets that IL-10 is produced almost exclusively by naive B cells while the proinflammatory cytokines lymphotoxin and TNF-α are largely produced by memory B cells. These results point to an in vivo switch in the cytokine “program” of human B cells transitioning from the naive pool to the memory pool. We propose a model that ascribes distinct and proactive roles to memory and naive human B cell subsets in the regulation of memory immune responses and in autoimmunity. Our findings are of particular relevance at a time when B cell directed therapies are being applied to clinical trials of several autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Distinct Effector Cytokine Profiles of Memory and Naive Human B Cell Subsets and Implication in Multiple Sclerosis

Duddy

Niino

Adatia

et al. 2007

The Journal of Immunology

584

594

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“…including MBP to the inflammation related to autoimmune reactions [43,[113][114][115]. Increased levels of Abs and oligoclonal IgGs in the cerebrospinal fluid together with clonal B cell accumulation in the CSF and lesions of MS patients are among the main evidences of MS [115].…”

Section: Lupus 70mentioning

confidence: 99%

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

Nevinsky¹

2017

Lupus

321

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Systemic lupus erythematosus (SLE) is known as a systemic polyethiologic diffuse autoimmune disease characterized by connective tissue disorganization and the paramount damage of skin and visceral capillaries. Usually, SLE symptoms include high fever, hair loss, mouth ulcers, chest pain, swollen lymph nodes, painful and swollen joints, increased fatigue, and appearance of red rash more often on the face. The exact reason of SLE appearance is not really clear. Detection of catalytic Abs (abzymes) was shown to be the earliest indicator of different AI disease development. Some abzymes are cytotoxic and can play a dangerous negative role in the pathogenesis of AI diseases. SLE is characterized by the appearance of abzymes with several different catalytic functions including hydrolysis of peptides and proteins, DNA, RNA, and oligosaccharides. In addition, monoclonal SLE abzymes are characterized by extraordinary diversity in the affinity to the substrates, physicochemical and catalytic characteristics, optimal conditions of catalysis, cytotoxicity, etc. Production of abzymes in SLE mice is associated with changes in the differentiation of hematopoietic stem cells of bone marrow, increase in lymphocyte proliferation, and significant suppression of cell apoptosis in different organs. In this chapter, abzymes with different catalytic activities in SLE are described.

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“…Many studies have identified autoantibodies directed against CNS antigens in MS patients (16,42,43). However, these anti-brain antibodies are not restricted to MS. For example, Traugott et al (44) detected anti-brain antibodies, as evidenced by their ability to stain oligodendrocytes or astrocytes from bovine or human brain sections, in 63% of MS sera, in 43% of patients with other neurological diseases (both inflammatory and noninflammatory) and in 29% of normal patients.…”

Section: Autoimmune Targetsmentioning

confidence: 99%

B cells in multiple sclerosis

Mark¹

2004

Front Biosci

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The most common laboratory abnormality in multiple sclerosis (MS) is an increased amount of cerebrospinal fluid IgG and the presence of oligoclonal bands. Despite studies of the humoral response that suggest the involvement of an infectious agent or autoantigen in disease, the major targets of the oligoclonal response are still unknown. Identification of these targets will reveal valuable insights into the cause and pathogenesis of MS and is likely to lead to effective treatment.

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B cells and antibodies in CNS demyelinating disease

Cited by 215 publications

References 133 publications

Distinct Effector Cytokine Profiles of Memory and Naive Human B Cell Subsets and Implication in Multiple Sclerosis

Distinct Effector Cytokine Profiles of Memory and Naive Human B Cell Subsets and Implication in Multiple Sclerosis

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

B cells in multiple sclerosis

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