BCMAp: an integral membrane protein in the Golgi apparatus of human mature B lymphocytes

Gras, Marjorie; Laâbi, Yacine; Linares-Cruz, Gustavo; Blondel, Marie-Odile; Rigaut, Jean Paul; Brouet, Jean‐Claude; Leca, Gérald; Haguenauer‐Tsapis, Rosine; Tsapis, Andréas

doi:10.1093/intimm/7.7.1093

Cited by 122 publications

(101 citation statements)

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“…16 BCMA staining was low on intact DLBCL tumor cells but significantly enhanced after permeabilization, confirming the presence of a major pool of BCMA in the Golgi apparatus. 37 In addition to BCMA, some DLBCL tumor cells express TACI, also consistent with previous data. 38 Hence, APRIL-R expression constitutes another level of heterogeneity in DLBCL tumor cells.…”

Section: Discussionsupporting

confidence: 91%

Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness

Schwaller

Schneider

Mhawech‐Fauceglia

et al. 2006

Blood

139

112

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High-grade lymphomas arising from mature B cells are constituted by Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). The latter represents the most common form of adult NHL. DLBCL is widely accepted for its heterogeneity, best reflected by differences in clinical responses to chemotherapy. 1 DLBCL heterogeneity was recently molecularly identified with gene-expression array studies. 2 Despite the significant improvement achieved in the therapy of this disease with the emergence of B-cell-specific (anti-CD20) monoclonal antibody treatment, resistant DLBCL remain a significant clinical problem. Indeed, the recent report analyzing the effect of chemotherapy combined with anti-CD20 indicates that 40% of patients do not survive in a 5-year follow-up period. 3 Future improvements to DLBCL therapy are therefore likely to result from the identification of key molecular targets in the treatmentresistant subtypes.APRIL (also known as TALL-2) and BAFF (also known as BLys, TALL-1) are closely related ligands of the TNF superfamily. They share 2 receptors, BCMA and TACI, whereas BAFF binds to a third receptor BAFF-R (also known as BR3). 4 BAFF-R, TACI, and BCMA are predominantly expressed on B cells, consistent with a role for these 2 TNF ligands in humoral immune responses. The BAFF/BAFF-R pathway is crucial for the maturation and maintenance of peripheral B cells. 5,6 BAFF participates also in humoral immune responses by providing B-cell costimulation and inducing Ig switch. 7,8 APRIL has no obvious role in B-cell development 9 but, like BAFF, is involved in humoral immune responses. 7,8,10 Dysregulation of the BAFF/APRIL pathways has been associated with several autoimmune diseases. 11 In addition to a role in autoimmune pathologies, APRIL and BAFF have been recently implicated in the development of tumors. 12 In animal models, APRIL and BAFF overexpression induces development of B-cell neoplasia. 13,14 The involvement of these 2 TNF ligands in B-cell tumors has been substantiated with in vitro studies on human cell lines. Exogenous APRIL confers a survival advantage to NHL, 15-17 and multiple myeloma. [18][19][20] Recently, APRIL binding to the heparan sulfate side chains of proteoglycans (HSPG) was demonstrated. 21,22 In contrast, BAFF does not bind HSPG, suggesting differences in APRIL and BAFF biology. Here, we analyzed in situ APRIL expression in human NHL. We observed that APRIL was only up-regulated in highgrade B-cell lymphomas and found that proteoglycans contribute to a tumor-promoting role of APRIL in these lymphomas. For personal use only. on May 9, 2018. by guest www.bloodjournal.org From Patients, materials, and methods Cells and reagentsAll culture media were RPMI-1640 supplemented with 10% FCS. The DLBCL lines SU-DHL-4 and -7 and OCI-Ly3, OCI-Ly7, and OCI-Ly10 were obtained from Dr A. Wiestner (NIH, Bethesda, MD). Dendritic cells were obtained from peripheral monocytes treated with GM-CSF/IL-4 as previously described. 23 Granulocytes were obtained from bone marrow CD34 ϩ cells as previously ...

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Section: Discussionsupporting

confidence: 91%

Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness

Schwaller

Schneider

Mhawech‐Fauceglia

et al. 2006

Blood

139

112

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“…An interesting result is the rare localization of BCMA on the cell membrane of ADMC. Indeed, usually, staining for BCMA is found intracellularly, located in the Golgi apparatus (12). In addition, Fn14 (the specific TWEAK receptor) is predominantly present at the membrane level in ADMC, whereas it translocates intracellularly in in vitro maturing adipocytes.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that APRIL, BAFF, and TWEAK possibly act on adipocytes precursors through these three receptors. It is notable that the observed BCMA membrane expression is rare, because this receptor is usually identified intracellularly (12).…”

Section: Effect Of Baff April and Tweak On Adipogenesismentioning

confidence: 99%

Adipocytes as Immune Cells: Differential Expression of TWEAK, BAFF, and APRIL and Their Receptors (Fn14, BAFF-R, TACI, and BCMA) at Different Stages of Normal and Pathological Adipose Tissue Development

Alexaki

Notas

Pelekanou

et al. 2009

The Journal of Immunology

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Adipose tissue represents a rich source of multipotent stem cells. Mesenchymal cells, isolated from this source, can differentiate to other cell types in vitro and therefore can be used for a number of regenerative therapies. Our view of adipose tissue has recently changed, establishing adipocytes as new members of the immune system, as they produce a number of proinflammatory cytokines (such as IL-6 and TNFα and chemokines, in addition to adipokines (leptin, adiponectin, resistin) and molecules associated with the innate immune system. In this paper, we report the differential expression of TNF-superfamily members B cell activating factor of the TNF Family (BAFF), a proliferation inducing ligand (APRIL), and TNF-like weak inducer of apoptosis (TWEAK) in immature-appearing and mature adipocytes and in benign and malignant adipose tissue-derived tumors. These ligands act through their cognitive receptors, BAFF receptor, transmembrane activator and calcium signal-modulating cyclophilic ligand (TACI), B cell maturation Ag (BCMA), and fibroblast growth factor-inducible 14 (Fn14), which are also expressed in these cells. We further report the existence of functional BCMA, TACI, and Fn14 receptors and their ligands BAFF, APRIL, and TWEAK on adipose tissue-derived mesenchymal cells, their interaction modifying the rate of adipogenesis. Our data integrate BAFF, APRIL, and TWEAK and their receptors BCMA, TACI, and Fn14 as novel potential mediators of adipogenesis, in addition to their specific role in immunity, and define immature and mature adipocytes as source of immune mediators.

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“…Surface expression of BCMA is absent or weak in most cells, and BCMA-null mice exhibit normal numbers of B cells as well as normal primary Ab responses to both TD and TI-II Ags (11,23,24). However, BCMA is more highly expressed on human plasmablasts and murine longlived plasma cells, and has recently been shown to enhance the survival of these cells (25,26).…”

Section: B Cell-activating Factor Belonging To the Tnf Family Acts Thmentioning

confidence: 99%

B Cell-Activating Factor Belonging to the TNF Family Acts through Separate Receptors to Support B Cell Survival and T Cell-Independent Antibody Formation

Shulga-Morskaya

Dobles

Walsh

et al. 2004

The Journal of Immunology

231

220

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The TNF-related ligand, B cell-activating factor belonging to the TNF family (BAFF), is necessary for normal B cell development and survival, and specifically binds the receptors transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), B cell maturation Ag (BCMA), and BAFF-R. Similarities between mice completely lacking BAFF and A/WySnJ strain mice that express a naturally occurring mutant form of BAFF-R suggest that BAFF acts primarily through BAFF-R. However, the nearly full-length BAFF-R protein expressed by A/WySnJ mice makes unambiguous interpretation of receptor function in these animals impossible. Using homologous recombination we created mice completely lacking BAFF-R and compared them directly to A/WySnJ mice and to mice lacking BAFF. BAFF-R-null mice exhibit loss of mature B cells similar to that observed in BAFF−/− and A/WySnJ mice. Also, mice lacking both TACI and BCMA simultaneously exhibit no B cell loss, thus confirming that BAFF-R is the primary receptor for transmitting the BAFF-dependent B cell survival signal. However, while BAFF-R-null mice cannot carry out T cell-dependent Ab formation, they differ from BAFF-deficient mice in generating normal levels of Ab to at least some T cell-independent Ags. These studies clearly demonstrate that BAFF regulates Ab responses in vivo through receptors in addition to BAFF-R.

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BCMAp: an integral membrane protein in the Golgi apparatus of human mature B lymphocytes

Cited by 122 publications

References 0 publications

Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness

Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness

Adipocytes as Immune Cells: Differential Expression of TWEAK, BAFF, and APRIL and Their Receptors (Fn14, BAFF-R, TACI, and BCMA) at Different Stages of Normal and Pathological Adipose Tissue Development

B Cell-Activating Factor Belonging to the TNF Family Acts through Separate Receptors to Support B Cell Survival and T Cell-Independent Antibody Formation

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