Study on the Mechanism of Selective Interaction of BR3 and BCMA with BAFF and APRIL

2020 ◽  
Vol 27 (11) ◽  
pp. 1114-1123 ◽  
Author(s):  
Luoman Li ◽  
Yaxin Jiang ◽  
LiLi Su ◽  
Deming Feng ◽  
Jing Wei ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Maturation ◽  
Binding Domains ◽  
B Cell Maturation ◽  
B Cell Activating Factor ◽  
Selective Interaction ◽  
Specific Antagonist ◽  
Specific Receptors ◽  
Α Helix ◽  
Selective Interactions

Background: B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) can activate signaling pathways by binding to specific receptors. BR3 (BAFF receptor) shows a unique selectivity for BAFF ligand, while B-cell maturation antigen (BCMA) exhibits a stronger interaction between APRIL-BCMA rather than BAFF-BCMA interaction. Objective: The combined domains were fused with IgG1 Fc to better understand which domain affects the selective interaction of the receptor with BAFF and APRIL. Methods: Since BR3 and BCMA both contain cysteine-rich repeat domains (CRD) with DxL motif, the binding domains of BR3 and BCMA were segmented into two parts in this study. BR3-1 (CFDLLVRHGVAC) and BCMA-1 (YFDSLLHACIPC) contained the conservative DxL motif, while BR3-2 (GLLRTPRPKPA) and BCMA-2 (QLRCSSNTPPLT) were adjacent to the CRDs yet still joined with BR3-1 and BCMA-1. Affinity between all possible combinations was then tested. Results: The affinity of BR3-1-BCMA-2-Fc and BR3-1-BR3-2-Fc for BAFF was higher than BCMA-1-BR3-2-Fc and BCMA-1-BCMA-2-Fc. Moreover, BR3-1-BCMA-2-Fc and BCMA-1-BCMA- 2-Fc had affinity for APRIL, while BR3-1-BR3-2-Fc and BCMA-1-BR3-2-Fc hardly interacted with APRIL. Conclusion: BR3-1 region played a key role for interaction with BAFF, while BCMA-1 region exhibited weaker binding with BAFF. BCMA-2 region having an α-helix might contribute towards selectivity of APRIL-BCMA binding and BR3-2 rigid region had deleterious effects on the APRIL-BR3 interaction. These results provide comprehensive insights of the mechanism of selective interactions, and may promote specific antagonist design in the future.

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.

Binding of B-cell maturation antigen to B-cell activating factor induces survival of multiple myeloma cells by activating Akt and JNK signaling pathways

2016 ◽  
Vol 34 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Xianjuan Shen ◽  
Yuehua Guo ◽  
Jing Qi ◽  
Wei Shi ◽  
Xinhua Wu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Signaling Pathways ◽  
Cell Maturation ◽  
Myeloma Cells ◽  
Jnk Signaling ◽  
B Cell Maturation ◽  
B Cell Activating Factor ◽  
B Cell Maturation Antigen

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.

Correlation of B cell activating factor, B cell maturation antigen, and other cytokines profile with inhibitor status in hemophilia A

2019 ◽  
Vol 44 (2) ◽  
pp. 149
Author(s):  
Nuzhat Husain ◽  
Sanya Arshad ◽  
Vandana Tiwari ◽  
Azfar Neyaz ◽  
NamrataP Awasthi
Keyword(s):  
B Cell ◽  
Hemophilia A ◽  
Cell Maturation ◽  
Factor B ◽  
B Cell Maturation ◽  
B Cell Activating Factor ◽  
B Cell Maturation Antigen

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 B Cell Maturation Antigen, the Receptor for a Proliferation-Inducing Ligand and B Cell-Activating Factor of the TNF Family, Induces Antigen Presentation in B Cells

2005 ◽  
Vol 175 (5) ◽  
pp. 2814-2824 ◽  
Author(s):  
Min Yang ◽  
Hidenori Hase ◽  
Diana Legarda-Addison ◽  
Leena Varughese ◽  
Brian Seed ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Antigen Presentation ◽  
Cell Maturation ◽  
B Cell Maturation ◽  
B Cell Activating Factor ◽  
B Cell Maturation Antigen

scholarly journals Targeted selection of HIV-specific antibody mutations by engineering B cell maturation

Science ◽  
2019 ◽  
Vol 366 (6470) ◽  
pp. eaay7199 ◽  
Author(s):  
Kevin O. Saunders ◽  
Kevin Wiehe ◽  
Ming Tian ◽  
Priyamvada Acharya ◽  
Todd Bradley ◽  
...  
Keyword(s):  
B Cell ◽  
Specific Antibody ◽  
Cell Maturation ◽  
B Cell Maturation ◽  
Selection Of
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