Targeting B cells and autoantibodies in the therapy of autoimmune diseases

Kao, Daniela; Lux, Anja; Schwab, Inessa; Nimmerjahn, Falk

doi:10.1007/s00281-014-0427-7

Cited by 13 publications

(6 citation statements)

References 103 publications

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“…Their ability to produce cytokines likely reflects their increasingly important role as regulatory cells of the immune system. Given the therapeutic success of B cell ablation (using anti-CD20 antibodies) in the treatment of human autoimmune diseases [130], we predict that the potential role of cytokine-producing B cells in human disease is a field that will yield many future surprises.…”

Section: B Cells As Cytokine Producersmentioning

confidence: 99%

B cells responses and cytokine production are regulated by their immune microenvironment

2015

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The adaptive immune system consists of two types of lymphocytes: T and B cells. These two lymphocytes originate from a common precursor, yet are fundamentally different with B cells mediating humoral immunity while T cells mediate cell mediated immunity. In cytokine production, naïve T cells produce multiple cytokines upon activation while naïve activated B cells do not. B cells are capable of producing cytokines, but their cytokine production depends on their differentiation state and activation conditions. Hence, unlike T cells that can produce a large amount of cytokines upon activation, B cells require specific differentiation and activation conditions to produce cytokines. Many cytokines act on B cells as well. Here, we discuss several cytokines and their effects on B cells including: Interleukins, IL-7, IL-4, IL-6, IL-10, and Interferons, IFN-α, IFN-β, IFN-γ. These cytokines play important roles in the development, survival, differentiation and/or proliferation of B cells. Certain chemokines also play important roles in B cell function, namely antibody production. As an example, we discuss CCL28, a chemokine that directs the migration of plasma cells to mucosal sites. We conclude with a brief overview of B cells as cytokine producers and their likely functional consequences on the immune response.

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Section: B Cells As Cytokine Producersmentioning

confidence: 99%

B cells responses and cytokine production are regulated by their immune microenvironment

2015

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“…An international, phase II study of belimumab to assess its efficacy in patients with AChR and MuSK MG with generalized disease is ongoing (NCT01480596). Other compounds targeting B cells or Bcell trophic factors are in development for autoimmune disease and could be also be investigated in MG [109].…”

Section: B Cells B-cell Trophic Factors and Plasma Cellsmentioning

confidence: 99%

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

2016

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Myasthenia gravis (MG) is an autoimmune disease associated with the production of autoantibodies against 1) the skeletal muscle acetylcholine receptor; 2) muscle-specific kinase, a receptor tyrosine kinase critical for the maintenance of neuromuscular synapses; 3) low-density lipoprotein receptor-related protein 4, an important molecular binding partner for muscle-specific kinase; and 4) other muscle endplate proteins. In addition to the profile of autoantibodies, MG may be classified according the location of the affected muscles (ocular vs generalized), the age of symptom onset, and the nature of thymic pathology. Immunopathologic events leading to the production of autoantibodies differ in the various disease subtypes. Advances in our knowledge of the immunopathogenesis of the subtypes of MG will allow for directed utilization of the ever-growing repertoire of therapeutic agents that target distinct nodes in the immune pathway relevant to the initiation and maintenance of autoimmune disease. In this review, we examine the pathogenesis of MG subtypes, current treatment options, and emerging new treatments and therapeutic targets.

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“…The role of B cells in autoimmune diseases is still only partially understood despite the well known literature linking linking autoantibodies to autoimmunity 26 . MS, in particular, is characterized by the presence of oligoclonal serum and CSF IgG bands, indicating that B lymphocytes are activated in this disease.…”

Section: Discussionmentioning

confidence: 99%

B Lymphocytes in Multiple Sclerosis: Bregs and BTLA/CD272 Expressing-CD19+ Lymphocytes Modulate Disease Severity

Piancone

Saresella

Marventano

et al. 2016

Sci Rep

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B lymphocytes contribute to the pathogenesis of Multiple Sclerosis (MS) by secreting antibodies and producing cytokines. This latter function was analyzed in myelin olygodendrocyte protein (MOG)-stimulated CD19+ B lymphocytes of 71 MS patients with different disease phenotypes and 40 age-and sex-matched healthy controls (HC). Results showed that: 1) CD19+/TNFα+, CD19+/IL-12+ and CD19+/IFNγ+ lymphocytes are significantly increased in primary progressive (PP) compared to secondary progressive (SP), relapsing-remitting (RR), benign (BE) MS and HC; 2) CD19+/IL-6+ lymphocytes are significantly increased in PP, SP and RR compared to BEMS and HC; and 3) CD19+/IL-13+, CD19+/IL-10+, and CD19+/IL-10+/TGFβ+ (Bregs) B lymphocytes are reduced overall in MS patients compared to HC. B cells expressing BTLA, a receptor whose binding to HVEM inhibits TcR-initiated cytokine production, as well as CD19+/BTLA+/IL-10+ cells were also significantly overall reduced in MS patients compared to HC. Analyses performed in RRMS showed that fingolimod-induced disease remission is associated with a significant increase in Bregs, CD19+/BTLA+, and CD19+/BTLA+/IL-10+ B lymphocytes. B lymphocytes participate to the pathogenesis of MS via the secretion of functionally-diverse cytokines that might play a role in determining disease phenotypes. The impairment of Bregs and CD19+/BTLA+ cells, in particular, could play an important pathogenic role in MS.

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Targeting B cells and autoantibodies in the therapy of autoimmune diseases

Cited by 13 publications

References 103 publications

B cells responses and cytokine production are regulated by their immune microenvironment

B cells responses and cytokine production are regulated by their immune microenvironment

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

B Lymphocytes in Multiple Sclerosis: Bregs and BTLA/CD272 Expressing-CD19+ Lymphocytes Modulate Disease Severity

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