Regulation of germinal center B‐cell differentiation

Zhang, Yang; Garcia-Ibanez, Laura; Toellner, Kai‐Michael

doi:10.1111/imr.12396

Cited by 142 publications

(151 citation statements)

References 105 publications

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“…Upon antigen recognition in the germinal center, B cells proliferate and differentiate (e.g. class switching) into a specific B cell for this antigen 27. In pSS, germinal centers are reported in the epithelium of non-lymphoid tissues such as the salivary glands 28.…”

Section: Pathogenesismentioning

confidence: 99%

“…Clinical risk factors include persistent, unilateral salivary gland enlargement, lymphadenopathy, splenomegaly, skin vasculitis, cryoglobulinemia and the development of glomerulonephritis 54, 55. Laboratory-assessed biological risk factors for lymphoma in pSS include cryoglobulinemia, lymphopenia (especially low total numbers of CD4+ T cells), hypocomplementia, increased serum BAFF and the presence of a monoclonal component in serum or urine 27, 54, 56. Articular involvement in pSS predominantly consists of symmetric, intermittent, nonerosive arthropathy 57, 58.…”

Section: Clinical Presentationmentioning

confidence: 99%

See 1 more Smart Citation

Reviewing primary Sjögren's syndrome: beyond the dryness - From pathophysiology to diagnosis and treatment

Both¹,

Dalm²,

Hagen³

et al. 2017

Int. J. Med. Sci.

178

110

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Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, characterized by lymphocytic infiltration of the secretory glands. This process leads to sicca syndrome, which is the combination of dryness of the eyes, oral cavity, pharynx, larynx and/or vagina. Extraglandular manifestations may also be prevalent in patients with pSS, including cutaneous, musculoskeletal, pulmonary, renal, hematological and neurological involvement. The pathogenesis of pSS is currently not well understood, but increased activation of B cells followed by immune complex formation and autoantibody production are thought to play important roles. pSS is diagnosed using the American-European consensus group (AECG) classification criteria which include subjective symptoms and objective tests such as histopathology and serology. The treatment of pSS warrants an organ based approach, for which local treatment (teardrops, moistures) and systemic therapy (including non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDS) and biologicals) can be considered. Biologicals used in the treatment of pSS mainly affect the total numbers of B cells (B cell depletion (Rituximab)) or target proteins required for B cell proliferation and/or activation (e.g. B cell activating factor (BAFF)) resulting in decreased B cell activity.The aim of this review is to provide physicians a general overview concerning the pathogenesis, diagnosis and management of pSS patients.

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Section: Pathogenesismentioning

confidence: 99%

Section: Clinical Presentationmentioning

confidence: 99%

Reviewing primary Sjögren's syndrome: beyond the dryness - From pathophysiology to diagnosis and treatment

Both¹,

Dalm²,

Hagen³

et al. 2017

Int. J. Med. Sci.

178

110

View full text Add to dashboard Cite

show abstract

“…For all GC B cells, Fas-mediated apoptosis is a potentially important factor, given the high expression of Fas on GC B cells. This is assumed to be crucial for affinity maturation in the light zone, which depends on antigen-dependent rescue of B cells with a high-affinity B cell receptor (BCR) [11–13] and removal of self-reactive B cells generated during somatic hypermutation (SHM). BCR-mediated signals might be needed to receive survival signals from T FH cells and possibly other GC cells.…”

Section: Update On the Major Conclusion Of The Ige-reporter-mouse Stmentioning

confidence: 99%

“…We will also ignore for the moment the diverse panel of inhibitors (cells and extracellular factors) that may modify the outcome of the interaction between the antigen and the B cell. For recent reviews on this topic, see for example [11–13]. …”

Section: Introductionmentioning

confidence: 99%

The Developmental History of IgE and IgG4 Antibodies in Relation to Atopy, Eosinophilic Esophagitis, and the Modified TH2 Response

Aalberse

Platts-Mills

Rispens

2016

Curr Allergy Asthma Rep

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A common reaction from anyone confronted with allergy is the question: what prevents universal allergy? We will discuss recent findings in the mouse system that have provided us with clues on why allergy is not more common. We will also address one crucial aspect of atopic allergy in humans, which is absent in most mouse model systems, an IgG/IgE ratio <10. We consider the typical mouse IgE response to be more closely related to the “modified TH2” response in humans. We will discuss the similarities and differences between the IgE and IgG4 response to allergens and an update on the IgG4 B cell, partly derived from studies on eosinophilic esophagitis and IgG4-related diseases.

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“…Effective humoral immune responses depend on germinal center (GC) reactions. Follicular B cells encounter antigen in the GC and receive T-cell help to differentiate into memory B cells and long-lived plasma cells that produce high-affinity antibodies (1). However, aberrant humoral immune responses against self-antigens lead to the development of autoimmune diseases.…”

Section: Lag3mentioning

confidence: 99%

Egr2 and Egr3 in regulatory T cells cooperatively control systemic autoimmunity through Ltbp3-mediated TGF-β3 production

Morita

Okamura

Inoue

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4 + regulatory T cells, CD4+ cells, that characteristically express both Egr2 and LAG3 and control mice model of lupus via TGF-β3 production. However, due to the mild phenotype of lymphocyte-specific Egr2-deficient mice, the presence of an additional regulator has been speculated. Here, we show that Egr2 and Egr3 expressed in T cells cooperatively prevent humoral immune responses by supporting TGF-β3 secretion. T cell-specific Egr2/Egr3 double-deficient (Egr2/3DKO) mice spontaneously developed an early onset lupus-like disease that was more severe than in T cell-specific Egr2-deficient mice. In accordance with the observation that CD4+ cells from Egr2/3DKO mice completely lost the capacity to produce TGF-β3, the excessive germinal center reaction in Egr2/3DKO mice was suppressed by the adoptive transfer of WT CD4+ cells or treatment with a TGF-β3-expressing vector. Intriguingly, latent TGF-β binding protein (Ltbp)3 expression maintained by Egr2 and Egr3 was required for TGF-β3 production from CD4+ cells. Because Egr2 and Egr3 did not demonstrate cell intrinsic suppression of the development of follicular helper T cells, Egr2-and Egr3-dependent TGF-β3 production by CD4+ cells is critical for controlling excessive B-cell responses. The unique attributes of Egr2/Egr3 in T cells may provide an opportunity for developing novel therapeutics for autoantibodymediated diseases including SLE.Egr2 | Egr3 | TGF-β3 | systemic lupus erythematosus | regulatory T cell

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Regulation of germinal center B‐cell differentiation

Cited by 142 publications

References 105 publications

Reviewing primary Sjögren's syndrome: beyond the dryness - From pathophysiology to diagnosis and treatment

Reviewing primary Sjögren's syndrome: beyond the dryness - From pathophysiology to diagnosis and treatment

The Developmental History of IgE and IgG4 Antibodies in Relation to Atopy, Eosinophilic Esophagitis, and the Modified TH2 Response

Egr2 and Egr3 in regulatory T cells cooperatively control systemic autoimmunity through Ltbp3-mediated TGF-β3 production

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