The Role of BAFF System Molecules in Host Response to Pathogens

Sakai, Jiro; Akkoyunlu, Mustafa

doi:10.1128/cmr.00046-17

Cited by 90 publications

(83 citation statements)

References 196 publications

(244 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…21,22 B cell-activating factor (BAFF) and proliferation-inducing ligand (APRIL) have been implicated in B-cell stimulation by dengue-infected CD14 + CD16 + monocytes, and, like dengue infection, R848 stimulates BAFF and APRIL production by monocytes. 21 BAFF and APRIL bind to BAFF family receptors that are expressed almost exclusively by B cells, 23 including BAFF-R and transmembrane activator and calciummodulator interactor TACI, 24 as well as B-cell maturation antigen (BCMA), which is mainly expressed by bone marrow plasma cells. 25 Therefore, we examined whether BAFF-R and TACI expression changes after B-cell stimulation with R848, and whether these changes are altered by the presence of monocytes.…”

Section: Cytokine Production In Naive and Memory B-cell Stimulation Cmentioning

confidence: 99%

Distinguishing naive‐ from memory‐derived human B cells during acute responses

et al. 2019

View full text Add to dashboard Cite

Objectives A fundamental question in influenza research is whether antibody titre decline upon successive exposure to variant strains is consequent to recall of cross‐reactive memory B cells that competitively inhibit naive B‐cell responses. In connection, it is not clear whether naive and memory B cells remain phenotypically distinct acutely after activation such that they may be distinguished ex vivo. Methods Here, we first compared the capacity of anti‐Ig and Toll‐like‐receptor (TLR) 7/8 and TLR9 agonists (R848 and CpG) to augment human B‐cell differentiation induced by IL‐21 and sCD40L. The conditions that induced optimal differentiation were then used to compare the post‐activation phenotype of sort‐purified naive and memory B‐cell subsets by FACS and antibody‐secreting cell (ASC) ELISPOT. Results Sort‐purified naive and memory B cells underwent robust plasmablast and ASC formation when stimulated with R848, but not CpG, and co‐cultured with monocytes. This coincided with increased IL‐1β and IL‐6 production when B cells were co‐cultured with monocytes and stimulated with R848, but not CpG. Naive B cells underwent equivalent ASC generation, but exhibited less class‐switch and modulation of CD27, CD38 and CD20 expression than memory B cells after stimulation with R848 and monocytes for 6 days. Conclusion Stimulation with R848, IL‐21 and sCD40L in the presence of monocytes induces robust differentiation and ASC generation from both naive and memory B‐cells. However, naive and memory B cells retain key phenotypic differences after activation that may facilitate ex vivo discrimination and better characterisation of acute responses to variant antigens.

show abstract

Section: Cytokine Production In Naive and Memory B-cell Stimulation Cmentioning

confidence: 99%

Distinguishing naive‐ from memory‐derived human B cells during acute responses

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In this study, we demonstrated that bacterial lipoproteins are major bacterial products with a strong BAFF-inducing capacity in DCs and also confirmed that indirect B-cell activating capacity of bacterial lipoproteins via BAFF production is beyond its direct effect. On the other hand, previous data from clinical and in vivo studies revealed increased expression levels of BAFF during bacterial infections by Mycoplasma pneumoniae , Mycobacterium tuberculosis , and Pseudomonas aeruginosa ( 68 ). In addition, increased levels of serum BAFF appear to correlate with disease severity in bacterial infectious diseases, such as tuberculosis ( 69 ).…”

Section: Discussionmentioning

confidence: 95%

“…In addition, increased levels of serum BAFF appear to correlate with disease severity in bacterial infectious diseases, such as tuberculosis ( 69 ). Since BAFF can promote inflammatory responses by inducing excessive Th1 and Th17 responses ( 16 , 68 ), BAFF production by bacterial lipoprotein might be closely related with progression and persistence of the bacterial infectious diseases. Moreover, bacterial lipoproteins have a potency to produce cytokines having BAFF-inducing ability, such as TNF-α and IL-10 ( 70 , 71 ), leading to synergistically enhanced BAFF production in DCs.…”

Section: Discussionmentioning

confidence: 99%

Bacterial Lipoproteins Induce BAFF Production via TLR2/MyD88/JNK Signaling Pathways in Dendritic Cells

Baik

Lee

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

B-cell activating factor (BAFF) plays a crucial role in survival, differentiation, and antibody secretion of B cells. Microbial products with B-cell mitogenic properties can indirectly promote expansion and activation of B cells by stimulating accessory cells, such as dendritic cells (DCs), to induce BAFF. Although bacterial lipoproteins are potent B-cell mitogen like lipopolysaccharides (LPSs), it is uncertain whether they can stimulate DCs to induce BAFF expression. Here, we evaluated the effect of bacterial lipoproteins on BAFF expression in mouse bone marrow–derived DCs. Lipoprotein-deficient Staphylococcus aureus mutant induced relatively low expression level of membrane-bound BAFF (mBAFF) and the mRNA compared with its wild-type strain, implying that bacterial lipoproteins can positively regulate BAFF induction. The synthetic lipopeptides Pam2CSK4 and Pam3CSK4, which mimic bacterial lipoproteins, dose-dependently induced BAFF expression, and their BAFF-inducing capacities were comparable to those of LPS in DCs. Induction of BAFF by the lipopeptide was higher than the induction by other microbe-associated molecular patterns, including peptidoglycan, flagellin, zymosan, lipoteichoic acid, and poly(I:C). Pam3CSK4 induced both mBAFF and soluble BAFF expression in a dose- and time-dependent manner. BAFF expression by Pam3CSK4 was completely absent in DCs from TLR2- or MyD88-deficient mice. Among various MAP kinase inhibitors, only JNK inhibitors blocked Pam3CSK4-induced BAFF mRNA expression, while inhibitors blocking ERK or p38 kinase had no such effect. Furthermore, Pam3CSK4 increased the DNA-binding activities of NF-κB and Sp1, but not that of C/EBP. Pam3CSK4-induced BAFF promoter activity via TLR2/1 was blocked by NF-κB or Sp1 inhibitor. Collectively, these results suggest that bacterial lipoproteins induce expression of BAFF through TLR2/MyD88/JNK signaling pathways leading to NF-κB and Sp1 activation in DCs, and BAFF derived from bacterial lipoprotein-stimulated DCs induces B-cell proliferation.

show abstract

“…Since their discovery in the mid‐1960s, B lymphocytes were mainly known for their ability to produce antibodies . The B‐cell‐derived antibody response has been reported to be critical to protect against microbial infections or mediate autoimmune diseases . Although the role of B cells in tumors is still conflicting and controversial, due to their antibody‐producing capacity, tumor‐infiltrating B cells are recognized as anti‐tumor immune components …”

Section: Introductionmentioning

confidence: 99%

Deceleration of glycometabolism impedes IgG‐producing B‐cell‐mediated tumor elimination by targeting SATB1

Liu

Zhou

et al. 2018

Immunology

View full text Add to dashboard Cite

B lymphocytes, known as antibody producers, mediate tumor cell destruction in the manner of antibody-dependent cell-mediated cytotoxicity; however, their anti-tumor function seems to be weakened during tumorigenesis, while the underlying mechanisms remain unclear. In this study, we found that IgG mediated anti-tumor effects, but IgG-producing B cells decreased in various tumors. Considering the underlying mechanism, glycometabolism was noteworthy. We found that tumor-infiltrating B cells were glucose-starved and accompanied by a deceleration of glycometabolism. Both inhibition of glycometabolism and deprivation of glucose through tumor cells, or glucose-free treatment, reduced the differentiation of B cells into IgG-producing cells. In this process, special AT-rich sequence-binding protein-1 (SATB1) was significantly silenced in B cells. Down-regulating SATB1 by inhibiting glycometabolism or RNA interference reduced the binding of signal transducer and activator of transcription 6 (STAT6) to the promoter of germline Cγ gene, subsequently resulting in fewer B cells producing IgG. Our findings provide the first evidence that glycometabolic inhibition by tumorigenesis suppresses differentiation of B cells into IgG-producing cells, and altering glycometabolism may be promising in improving the anti-tumor effect of B cells.

show abstract

The Role of BAFF System Molecules in Host Response to Pathogens

Cited by 90 publications

References 196 publications

Distinguishing naive‐ from memory‐derived human B cells during acute responses

Distinguishing naive‐ from memory‐derived human B cells during acute responses

Bacterial Lipoproteins Induce BAFF Production via TLR2/MyD88/JNK Signaling Pathways in Dendritic Cells

Deceleration of glycometabolism impedes IgG‐producing B‐cell‐mediated tumor elimination by targeting SATB1

Contact Info

Product

Resources

About