scholarly journals Maturation of Marginal Zone and Follicular B Cells Requires B Cell Activating Factor of the Tumor Necrosis Factor Family and Is Independent of B Cell Maturation Antigen

2001 ◽  
Vol 194 (11) ◽  
pp. 1691-1698 ◽  
Author(s):  
Pascal Schneider ◽  
Hisakazu Takatsuka ◽  
Anne Wilson ◽  
Fabienne Mackay ◽  
Aubry Tardivel ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Tumor Necrosis ◽  
Marginal Zone ◽  
Cell Maturation ◽  
Soluble Form ◽  
B Cell Maturation ◽  
B Cell Activating Factor ◽  
Necrosis Factor ◽  
B Cell Maturation Antigen

B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.

scholarly journals Baff Binds to the Tumor Necrosis Factor Receptor–Like Molecule B Cell Maturation Antigen and Is Important for Maintaining the Peripheral B Cell Population

2000 ◽  
Vol 192 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Jeffrey S. Thompson ◽  
Pascal Schneider ◽  
Susan L. Kalled ◽  
LiChun Wang ◽  
Eric A. Lefevre ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Cell Population ◽  
Tumor Necrosis ◽  
Cell Maturation ◽  
Soluble Form ◽  
B Cell Maturation ◽  
Necrosis Factor ◽  
B Cell Maturation Antigen

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor–triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

scholarly journals TACI and BAFF-R mediate isotype switching in B cells

2005 ◽  
Vol 201 (1) ◽  
pp. 35-39 ◽  
Author(s):  
Emanuela Castigli ◽  
Stephen A. Wilson ◽  
Sumi Scott ◽  
Fatma Dedeoglu ◽  
Shengli Xu ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Maturation ◽  
Isotype Switching ◽  
B Cell Maturation ◽  
Human B Cells ◽  
Necrosis Factor ◽  
B Cell Maturation Antigen

The tumor necrosis factor family members BAFF and APRIL induce Ig isotype switching in human B cells. We analyzed the ability of BAFF and APRIL to induce isotype switching in murine B cells to IgG1, IgA, and IgE. APRIL and BAFF each engage two receptors, transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), on B cells. In addition, BAFF engages a third receptor on B cells, BAFF-R. To determine the role of these receptors in isotype switching, we examined B cells from mice deficient in TACI, BCMA, and BAFF-R. The results obtained indicate that both TACI and BAFF-R are able to transduce signals that result in isotype switching.

scholarly journals A Soluble Form of B Cell Maturation Antigen, a Receptor for the Tumor Necrosis Factor Family Member April, Inhibits Tumor Cell Growth

2000 ◽  
Vol 192 (11) ◽  
pp. 1677-1684 ◽  
Author(s):  
Paul Rennert ◽  
Pascal Schneider ◽  
Teresa G. Cachero ◽  
Jeffrey Thompson ◽  
Luciana Trabach ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Necrosis ◽  
Cell Maturation ◽  
Soluble Form ◽  
Tumor Cell Growth ◽  
B Cell Maturation ◽  
Necrosis Factor ◽  
B Cell Maturation Antigen

A proliferation-inducing ligand (APRIL) is a ligand of the tumor necrosis factor (TNF) family that stimulates tumor cell growth in vitro and in vivo. Expression of APRIL is highly upregulated in many tumors including colon and prostate carcinomas. Here we identify B cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI), two predicted members of the TNF receptor family, as receptors for APRIL. APRIL binds BCMA with higher affinity than TACI. A soluble form of BCMA, which inhibits the proliferative activity of APRIL in vitro, decreases tumor cell proliferation in nude mice. Growth of HT29 colon carcinoma cells is blocked when mice are treated once per week with the soluble receptor. These results suggest an important role for APRIL in tumorigenesis and point towards a novel anticancer strategy.

scholarly journals Expression of B-cell activating factor, a proliferating inducing ligand and its receptors in primary central nervous system lymphoma

2013 ◽  
Vol 5 (1) ◽  
pp. 4 ◽  
Author(s):  
Tobias Birnbaum ◽  
Sigrid Langer ◽  
Sigrun Roeber ◽  
Louisa Von Baumgarten ◽  
Andreas Straube
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Central Nervous System Lymphoma ◽  
Cell Maturation ◽  
B Cell Maturation ◽  
B Cell Activating Factor ◽  
Autocrine Stimulation ◽  
Necrosis Factor ◽  
Stimulation Of

B-cell activating factor belonging to the tumor necrosis factor family (BAFF) and a proliferating inducing ligand (APRIL) might play an important role in the pathogenesis of systemic B-cell malignancies. However, the BAFF/APRIL system has not been systematically evaluated in primary central nervous system lymphoma (PCNSL) to date. We assessed the expression of BAFF, APRIL and its receptors BAFF-R (BAFF receptor), BCMA (B-cell maturation antigen) and TACI (transmembrane activator and calcium modulator cyclophilin ligand interactor) in five PCNSL specimens by immunohistochemical staining. We found extensive expression of BAFF and weak to moderate expression of APRIL, BAFF-R, BCMA, and TACI in all specimens. CD20 positive cells showed expression of both ligands and receptors at the same time. Our results indicate that autocrine stimulation of the BAFF/APRIL system might be involved in the pathogenesis of PCNSL.

scholarly journals B-Cell Maturation Antigen, A Proliferation-Inducing Ligand, and B-Cell Activating Factor Are Candidate Mediators of Spinal Cord Injury-Induced Autoimmunity

2013 ◽  
Vol 30 (6) ◽  
pp. 434-440 ◽  
Author(s):  
Jonah W. Saltzman ◽  
Ricardo A. Battaglino ◽  
Loise Salles ◽  
Prateek Jha ◽  
Supreetha Sudhakar ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
B Cell ◽  
Cell Maturation ◽  
B Cell Maturation ◽  
B Cell Activating Factor ◽  
Cord Injury ◽  
Antigen A ◽  
B Cell Maturation Antigen

scholarly journals Treatment of Autoimmune Hyperthyroidism in a Murine Model of Graves’ Disease with Tumor Necrosis Factor-Family Ligand Inhibitors Suggests a Key Role for B Cell Activating Factor in Disease Pathology

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4561-4568 ◽  
Author(s):  
Jacqueline A. Gilbert ◽  
Susan L. Kalled ◽  
Jane Moorhead ◽  
Donna M. Hess ◽  
Paul Rennert ◽  
...  
Keyword(s):  
B Cell ◽  
Plasma Cells ◽  
Autoimmune Disorder ◽  
Cell Maturation ◽  
Graves Disease ◽  
Histopathological Analysis ◽  
Specific Receptor ◽  
B Cell Maturation ◽  
B Cell Activating Factor ◽  
B Cell Maturation Antigen

Hyperthyroid Graves’ disease is a common autoimmune disorder mediated by agonistic antibodies to the TSH receptor, termed thyroid stimulating antibodies (TSAbs). Recently members of the TNF superfamily, B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), have been identified along with their receptors, B cell maturation antigen and transmembrane activator and calcium-modulator and cyclophilin ligand interactor, and the BAFF-specific receptor. BAFF is a fundamental B cell survival/maturation factor, and both BAFF and APRIL have been implicated in antibody production. We investigated the effect of interfering with BAFF- and APRIL-mediated signals in an induced model of Graves’ disease by blockade of these factors using soluble decoy receptors. In a therapeutic setting in mice with established hyperthyroidism, we show that blockade of BAFF or BAFF+APRIL with BAFF-specific receptor-Fc and B cell maturation antigen-Fc, respectively, leads to significant reductions in the induced hyperthyroidism. This was supported by a parallel pattern of declining TSAbs in the responding animals. Histopathological analysis of splenic sections from treated animals revealed marked reductions in the B cell follicle regions, but staining with anti-CD138 revealed the persistence of plasma cells. Thus, the reductions in TSAbs in the treated animals were not related to overall plasma cell numbers in the secondary lymphoid organs. Our results are the first to demonstrate attenuation of established hyperthyroidism by therapeutic intervention aimed at autoreactive B cells and indicate that both BAFF and APRIL appear to play important roles in the development and survival of the autoantibody producing cells in this model.

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