BAFF, APRIL and human B cell disorders

Tangye, Stuart G.; Bryant, Vanessa L.; Cuss, Amanda K.; Good, Kim L.

doi:10.1016/j.smim.2006.04.004

Cited by 184 publications

(156 citation statements)

References 130 publications

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“…SLE disease is also characterized by sustained lymphocyte stimulation, based on a high CD154 expression on T cells (Toubi and Shoenfeld 2004b) as well as an increased concentration of BAFF (Tangye et al 2006;Zhang et al 2001). Based on these studies, we further investigated the effect of IVIg treatment on B cells were stimulated as described in Fig.…”

Section: Ivig Treatment Increases the Proportion Of 9g4 + Cells In Slmentioning

confidence: 99%

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

Néron

Boire

Dussault

et al. 2009

Arch. Immunol. Ther. Exp.

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Introduction: Aberrant signaling within and between B and T cells, considered to be central in systemic lupus erythematosus (SLE), could depend on enhanced CD40-CD154 activation. As a result, autoreactive B cells, normally anergic, differentiate and secrete antibodies attacking several normal tissues. Thus restorating B cell homeostasis might help control this disease. In this study, two facets of SLE B cells were investigated, namely their in vitro response to CD40-CD154 and the effect of treatment with human immunoglobulins for intravenous use (IVIg). Materials and Methods: Blood samples from SLE patients and healthy volunteers were obtained and used to isolate B cells, which were activated through CD40 in the presence or absence of IVIg. The phenotype, proliferation, and differentiation of the SLE B cells were determined and compared with those of control B cells using flow cytometry and standard ELISA. Results: In this model, CD40-activated SLE B cells, as control B cells, proliferated and differentiated and were characterized by the emergence of CD19 lo CD38 ++ CD138 + CD27 ++ cells. IVIg treatment of the CD40-activated SLE B cells resulted in higher differentiation, characterized by increased secretion rates of IgG and IgM, as reported previously for control B cells. Conclusions: Taken as a whole, such accelerated differentiation of CD40-activated B cells suggests that IVIg may participate in re-equilibration of the antibody repertoire by replacing pathological antibodies by de novo harmless antibodies.

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Section: Ivig Treatment Increases the Proportion Of 9g4 + Cells In Slmentioning

confidence: 99%

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

Néron

Boire

Dussault

et al. 2009

Arch. Immunol. Ther. Exp.

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“…APRIL also binds to heparin sulfate proteoglycan structures [56]. Dysregulation of BAFF and/or its receptors has been associated with a variety of human B cell disorders, including autoimmunity, malignancy, and immunodeficiency [57]. However, the signal transduction pathways of BAFF and its receptors in B cells are still being elucidated.…”

Section: Receptors For Baff and Aprilmentioning

confidence: 99%

Roles of TRAF molecules in B lymphocyte function

Xie

Kraus

Stunz

et al. 2008

Cytokine & Growth Factor Reviews

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Tumor necrosis factor receptor associated factors (TRAFs) play a variety of interesting and important roles in the regulation of B lymphocyte function. They act both as cytoplasmic regulatory molecules, and as signal transducers for receptors involved in both innate and adaptive humoral immune responses. In this brief review, we highlight the current state of knowledge of the diverse roles of TRAF molecules in the functions of B lymphocytes. CD40CD40 is the most well-studied member of the TNFR superfamily expressed by B lymphocytes, so its interactions with TRAF molecules have also been intensively investigated. B cell CD40 is important in the induction of B cell survival and expansion, immunoglobulin (Ig) production and isotype switching, upregulation of surface molecules involved in B cell antigen presentation, differentiation to B memory cells, and the production of various cytokines (reviewed in [1]. The TRAF molecules have been shown to contribute to each of these functions (reviewed in [2].In 1994, TRAF3 became the first cytoplasmic molecule demonstrated to associate with CD40 (reviewed in [2]). However, for many years, its roles in CD40 signaling were largely unknown, and are still not completely understood. TRAF3 -/-mice die shortly after birth, but adoptive transfer of fetal liver cells from these mice suggested that their B cells were capable of reconstituting the humoral response [3], implying that TRAF3 is not required to promote CD40-mediated antibody responses. This conclusion was supported by experiments in B cell lines demonstrating that inducible overexpression of TRAF3 inhibits both CD40 responses [4], and cooperation between CD40 and the BCR [5]. Subsequently, B cell lines made completely TRAF3-deficient via gene targeting by homologous recombination show no defects in CD40 signaling overall, and display enhanced CD40-mediated c-jun kinase (JNK) activation and IgM production [6]. Recently, mice made conditionally deficient in TRAF3 only in CD19+ B cells show no deficiencies in CD40 signaling in vitro and have enhanced antibody responses [7]. TRAF2 was initially demonstrated to bind CD40 by exogenous overexpression studies in adenocarcinoma cell lines, in which it promotes JNK activation and the activity of NF-κB reporter genes (reviewed in [2]. Because TRAF2 -/-mice have an early lethal phenotype [8],Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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“…APRIL is highly expressed in tumors of various origins and poorly expressed in normal cells (16). The serum levels of BAFF and APRIL are elevated in patients with systemic lupus erythematosus (SLE) (17).…”

Section: Introductionmentioning

confidence: 99%

Age-related changes in BAFF and APRIL profiles and upregulation of BAFF and APRIL expression in patients with primary antibody deficiency

Jin

Kaneko²,

Suzuki³

et al. 2008

Int J Mol Med

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Abstract. In some patients with common variable immunodeficiency (CVID) and immunoglobulin (Ig) A deficiency (IgAD), tumor necrosis factor (TNF) family receptor transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) gene mutations have been reported. B cells from individuals with TACI mutations do not produce IgG and IgA in response to the TACI ligand a proliferation-inducing ligand (APRIL) which probably suggests impaired isotype switching. To clarify the pathogenesis of CVID and IgAD of Japanese patients, we investigated the mutations of TNF family members TACI, APRIL, B-cell activating factor (BAFF), B-cell maturation antigen (BCMA) and BAFF receptor (BAFF-R) genes and the expression levels of BAFF and APRIL in patients with CVID, IgAD and X-linked agammaglobulinaemia (XLA). We also investigated the relationship between age and the blood plasma levels of BAFF and APRIL. The causative gene mutations of TNF family members in our patients were not detected. In healthy subjects, the BAFF and APRIL plasma levels correlated inversely with age. The BAFF and APRIL plasma levels of patients with CVID, IgAD and XLA were significantly higher than those of healthy children. Elevated BAFF and APRIL expression levels might partially reflect the common immunological feature of primary antibody deficiency.

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BAFF, APRIL and human B cell disorders

Cited by 184 publications

References 130 publications

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

Roles of TRAF molecules in B lymphocyte function

Age-related changes in BAFF and APRIL profiles and upregulation of BAFF and APRIL expression in patients with primary antibody deficiency

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