b cell activating factor
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Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 45
Author(s):  
Marko Kumric ◽  
Piero Marin Zivkovic ◽  
Tina Ticinovic Kurir ◽  
Josip Vrdoljak ◽  
Marino Vilovic ◽  
...  

As early commencement of inflammatory bowel disease (IBD) treatment has been shown to substantially improve outcomes, it is of utmost importance to make a timely diagnosis of this disease. Despite undisputed sensitivity of fecal calprotectin, the most widely accepted IBD biomarker, in discriminating between irritable bowel syndrome (IBS) and IBD, as well as recognized role in monitoring disease activity and response to therapy, perhaps the biggest setback of calprotectin use in IBD is lack of specificity. Therefore, an additional biomarker in IBD is warranted. B-cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily, recently emerged as a viable candidate for this role. So far, overproduction of BAFF has been observed in various autoimmune diseases, most notably in systemic lupus erythematosus, where BAFF-inhibitor belimumab was approved for treatment. As BAFF levels were also shown to correlate with indices of IBD, in this review we aimed to summarize the current evidence with respect to the role of BAFF in diagnosis and assessing the activity of IBD, as well as putative therapeutic implications that may arise from exploring of this relation.


Author(s):  
Yidan Zhang ◽  
Jie Tian ◽  
Fan Xiao ◽  
Leting Zheng ◽  
Xiaoxia Zhu ◽  
...  

2021 ◽  
Author(s):  
Violeta Block ◽  
Eirini Sevdali ◽  
Mike Recher ◽  
Hassan Abolhassani ◽  
Lennart Hammarstrom ◽  
...  

Abstract Purpose B cell activating factor (BAFF) binding to BAFF-receptor(BAFFR) activates essential cellular functions required forthe survival of mature, human B cells. Thus,deletion ofthe BAFFR gene blocks the development of B cells at the transition from immature to mature B cells resulting in B lymphopenia and hypogammaglobulinemia. In addition to complete BAFFR deficiency, single nucleotide variants changing the primary amino acid sequence of BAFFR gene exist. Some of these variants were foundin patients suffering from immunodeficiency, autoimmunity, or B cell lymphomas. However, it remains unclearto which extent such variants disturb the activity of BAFFR. Methods Since individual differences and genetic/environmental modifiers change the expression and activity of BAFFR, we developed a cellular system that allows the unbiased analysis of BAFFR variants P21R, A52T, G64V, Dup92-95, P146S, and H159Y regarding oligomerization, signaling, and ectodomain shedding.Results Here we show that several of these variants impair BAFFR oligomerization, direct interactions between BAFFR and the B cell receptor component CD79B, BAFFR ectodomain shedding and the activation of AKT and ERK1/2. Conclusion All of these variants are pathogenic and have the potential to contribute to the development of primary antibody deficiencies, autoimmunity and lymphoma, but they most likely do not cause B lymphopenia and agammaglobulinemia like complete BAFFR deficiency.


mBio ◽  
2021 ◽  
Author(s):  
Tsai-Ling Liao ◽  
Yi-Ming Chen ◽  
Shie-Liang Hsieh ◽  
Kuo-Tung Tang ◽  
Der-Yuan Chen ◽  
...  

HCV remains an important cause of liver disease worldwide. Accumulating evidence has demonstrated that HCV infection is associated with B cell lymphoproliferative disorders such as MC.


PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0259158
Author(s):  
Runa Kuley ◽  
Kevin E. Draves ◽  
Deborah H. Fuller ◽  
Natalia V. Giltiay ◽  
Edward A. Clark ◽  
...  

Mice lacking B cells are more susceptible to S. typhimurium infection. How B cells contribute to protective immunity against Salmonella and what signals drive their activation are still unclear. Neutrophils (Nphs), monocytes (MOs), and dendritic cells (DCs) are involved in early immune responses to control the initial replication of S. typhimurium. These cells can produce B cell activating factor (BAFF) required for mature B cell survival and may help regulate B cell responses during Salmonella infection. Using BAFF reporter mice (BAFF-RFP+/-), we discovered that an i.p. infection with a virulent strain of S. typhimurium increased BAFF expression in splenic conventional DCs (cDC) and inflammatory Ly6Chi MOs/DCs four days post-infection. S. typhimurium infection induced the release of BAFF from Nphs, a decrease of BAFF-RFP expression and expansion of BAFF-RFP+ Nphs in the spleen and peritoneal cavity. After S. typhimurium infection, serum BAFF levels and immature and mature B cell subsets and plasma cells increased substantially. Conditional knockout (cKO) mice lacking BAFF in either Nphs or cDCs compared to control Bafffl/fl mice had reduced up-regulation of systemic BAFF levels and reduced expansion of mature and germinal center B cell subsets after infection. Importantly, the cKO mice lacking BAFF from either Nphs or cDCs had impaired induction of Salmonella-specific IgM Abs, and were more susceptible to S. typhimurium infection. Thus, Nphs and cDCs are major cellular sources of BAFF driving B cell responses, required for mounting optimal protective immunity against lethal Salmonella infection.


Author(s):  
Akey Krishna Swaroop ◽  
Chaitanya MVNL ◽  
Meena S ◽  
Gomathy Subramanian ◽  
Jawahar Natarajan ◽  
...  

The concept of immunomodulation was proposed by Edward Jenner, while working on polio vaccine in 1796. Many of the autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, psoriatic arthritis and system lupus erythematosus, viral diseases and, some cancers are characterized with elevated levels of "immunocytokine" gene expression, including, tumor necrosis factor-α, various interleukins, cytotoxic T-cell antigen-4, B-cell activating factor. For the treatment of these diseases, the immunologically-based therapies play the major role. In these lines, the usage of phytomedicines as immunostimulants /immunosuppressants have been enhanced considerably in last few decades and also used as a prophylactic treatment for various ailments. Phytochemicals such as flavonoids, terpenoids, polysaccharides, lactones, alkaloids, glycosides and saponins present in several plants, have been confirmed to exhibit immunomodulating properties. This review focuses on the traditional plants and their constituents which have been extensively used as immunomodulators. We have also highlighted the mechanism of action (MOA) of these plant constituents related to autophagy and adjuvanticity of drugs.


2021 ◽  
Vol 43 ◽  
pp. S224-S225
Author(s):  
JO Frade-Guanaes ◽  
AP Racanelli ◽  
LH Siqueira ◽  
C Costa-Lima ◽  
SS Medina ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lixia Wang ◽  
Tianyi Zhang ◽  
Zheng Zhang ◽  
Zihan Wang ◽  
Yu-Jie Zhou ◽  
...  

Abstract Background B cell activating factor (BAFF) is a member of the tumor necrosis factor (TNF) superfamily with immunomodulatory effects on both innate and adaptive immune responses. Periodontitis is an inflammatory disease characterized by periodontal soft tissue inflammation and the progressive loss of periodontal ligament and alveolar bone. Macrophages are closely related to periodontitis progression. However, the role of BAFF in periodontitis development and macrophage polarization and the underlying mechanism remain unknown. Methods In vivo, a ligation-induced mouse model of periodontitis for BAFF blockade was established to investigate the expression of inducible nitric oxide synthase (iNOS) through real-time PCR (RT-PCR) and immunohistochemistry. In addition, the level of TNF-α in the periodontium, the number of osteoclasts, and alveolar bone resorption were observed. In vitro, RAW 264.7 macrophage cells were treated with 100 ng/mL Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) in either the presence or absence of 50 nM small interfering RNA (siRNA) targeting BAFF, followed by further incubation for 24 h. These cells and supernatants were collected and stored for RT-PCR, enzyme-linked immunosorbent assay, western blotting and immunofluorescence microscopy. Results In vivo, BAFF blockade decreased the levels of TNF-α in the periodontium in a ligature-induced mouse periodontitis model. Reduced osteoclast formation and lower alveolar bone loss were also observed. In addition, BAFF blockade was related to the expression of polarization signature molecules in macrophages. In vitro, BAFF knockdown notably suppressed the production of TNF-α in RAW 264.7 cells stimulated by P. gingivalis LPS. Moreover, BAFF knockdown attenuated the polarization of RAW 264.7 cells into classically activated macrophages (M1), with reduced expression of iNOS. Conclusions Based on our limited evidence, we showed BAFF blockade exhibits potent anti-inflammatory properties in mice experimental periodontitis in vivo and in P. gingivalis LPS-treated RAW 264.7 cells in vitro, and macrophage polarization may be responsible for this effect.


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