BAFF selectively enhances the survival of plasmablasts generated from human memory B cells

Avery, Danielle T.; Kalled, Susan L.; Ellyard, Julia I.; Ambrose, Christine; Bixler, Sarah A.; Thien, Marilyn; Brink, Robert; Mackay, Fabienne; Hodgkin, Philip D.; Tangye, Stuart G.

doi:10.1172/jci18025e1

Cited by 78 publications

(142 citation statements)

References 37 publications

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“…19,20 TACI binds to not only the B-cellactivating factor (BAFF) encoded by TNFSF13B, but also the second ligand called a proliferative inducing ligand (APRIL) encoded by TNFSF13. 21 These interactions induce class switch recombination in human and murine B cells.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Liao

Zhang

et al. 2012

Genes Immun

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IgG has a crucial role in humoral immune response. Serum IgG level is mainly determined under genetic control. To explore the genetic influence on serum IgG levels, a two-stage genome-wide association study (GWAS) was performed in a healthy Chinese population of 3495 men, including 1999 unrelated subjects in the first stage and 1496 independent individuals in the second stage. Three single-nucleotide polymorphisms (SNPs) located in TNFRSF13B on 17p11.2 or nearby were significantly associated with IgG level: rs4792800 in the intron (combined P-value ¼ 1.45 Â 10 À 12 ), rs12603708 in the intron (combined P-value ¼ 1.82 Â 10 À 8 ) and rs3751987 at B65 kb downstream of the 5 0 -UTR region of TNFRSF13B (combined P-value ¼ 3.67 Â 10 À 9 ). Additionally, smoking was identified to be associated with IgG level in both stages (Po0.001), but there was no significant interaction between smoking and the identified SNPs (P40.05). The strong association between variants at TNFRSF13B and IgG level may be helpful to further explore the biological mechanism by which the serum IgG is affected by transmembrane activator, calcium modulator and cyclophilin ligand interactor encoded by TNFRSF13B.Genes and Immunity (2012) 13, 509-513; doi:10.1038/gene.2012.26; published online 7 June 2012Keywords: IgG; genome-wide association studies; TNFRSF13B; TACI; smoking INTRODUCTION IgG, constituting some 80% of total serum immunoglobulin, is the most abundant class of antibodies (Ab) in serum and extracellular fluid. It has an important role in the defense against various pathogens, toxins and even cancers. 1 As the only isotype that can pass through the human placenta, IgG is able to protect the fetus in utero. 2 Meanwhile, IgG gets involved in chronic inflammatory processes contributed to the destruction of healthy tissues in autoimmune diseases, such as arthritis and systemic lupus erythematosus. 3 Serum IgG level varies considerably from one person to another, 4 but little when testing the same person repeatedly. 5 This variation in the serum IgG concentration reflects the balance among the rates of synthesis and catabolism. 6 Multitudinous environmental factors including infections, smoking and chemical compounds can contribute to this variation. 7-9 Reports of pedigree studies or twin studies 10,11 have shown that genetic factors are more important than environmental exposures in determining serum immunoglobulin level in human. 12,13 The values of genetic heritability was h 2 ¼ 0.617 þ 0.020 for IgG. 6 Besides, several studies in a population of common variable immunodeficiency patients or IgA deficiency patients implied that there might be an association between some gene loci and serum IgG level. 14,15 However, to the best of our knowledge, no study has ever been conducted to identify the immune loci directly involved in the regulation of the IgG level.Genome-wide association study (GWAS) is a powerful and unbiased tool for the identification of common genetic variants associated with complex traits. 16 This hypothesis-free approach base...

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Liao

Zhang

et al. 2012

Genes Immun

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“…Continued expression of these chemokines as virus is cleared may sustain ongoing recruitment as ASC continue to emerge from lymphoid organs. The elevated level of BAFF mRNA within the CNS supports induction of factors necessary for prolonged ASC survival [54]. Furthermore, in contrast to ASC apoptosis within inflammatory lesions following virus clearance from peripheral tissues, few apoptotic cells are detected in the CNS [55], and ASC are retained in apparent preference to BM.…”

Section: Discussionmentioning

confidence: 99%

CNS viral infection diverts homing of antibody‐secreting cells from lymphoid organs to the CNS

et al. 2006

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Neurotropic coronavirus infection of mice results in acute encephalomyelitis followed by viral persistence. Whereas cellular immunity controls acute infection, humoral immunity regulates central nervous system (CNS) persistence. Maintenance of serum Ab was correlated with tissue distribution of virus-specific Ab-secreting cells (ASC). Although virus-specific ASC declined in cervical lymph node and spleen after infectious virus clearance, virus-specific serum Ab was sustained at steady levels, with a delay in neutralizing Ab. Virus-specific ASC within the CNS peaked rapidly 1 wk after control of infectious virus and were retained throughout chronic infection, consistent with intrathecal Ab synthesis. Surprisingly, frequencies of ASC in the BM remained low and only increased gradually. Nevertheless, virus-specific ASC induced by peripheral infection localized to both spleen and BM. The data suggest that CNS infection provides strong stimuli to recruit ASC into the inflamed tissue through sustained up-regulation of the CXCR3 ligands CXCL9 and CXCL10. Irrespective of Ag deprivation, CNS retention of ASC coincided with elevated BAFF expression and ongoing differentiation of class II + to class II -CD138 + CD19 + plasmablasts. These results confirm the CNS as a major ASCsupporting environment, even after resolution of viral infection and in the absence of chronic ongoing inflammation. IntroductionThe preeminent goal of the immune system is to eliminate pathogens and establish immunological memory [1]. Both T cells and Ab participate in eliminating a variety of pathogens; however, sustained serum Ab is an important criteria for many vaccination strategies, as they provide the first line of defense against re-infection [2]. Upon Ag encounter in regional lymph nodes, B cells undergo clonal expansion in extrafollicular foci and within germinal centers [3,4].Rapidly activated B cells secrete low-affinity Ab but can undergo isotype switching and limited BCR hypermutation as they differentiate into plasmablasts [3]. In the milieu of accessory cells and cytokines, germinal center B cells undergo affinity maturation and ultimately differentiate into both Ab-secreting cells (ASC) and memory B cells. As Ag is depleted, ASC and memory B cells are detected with increasing frequency in BM [2], where both stromal cells and other resident cells provide soluble as well as contact-dependent survival signals, including CXCL12 and BAFF [5]. Ab secretion by terminally differentiated plasma cells is independent of both Ag and T cell regulation [2,6]. Long-lived ASC in BM and spleen maintain serum Ab, thus providing protective immunity to re-infection, sometimes for the [4,6]. In contrast to Ag encountered in the periphery, the regulation of B cell activation by Ag sequestered within the central nervous system (CNS) is less clear. The absence of dedicated lymphatic drainage and the presence of the blood brain barrier (BBB) limits Ag transport from the CNS into secondary lymphoid tissue as well as trafficking of both cells and macromolecule...

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“…T cells then differentiate into effective cells preferentially producing Th1 cytokines (23). And the BAFF on T cells may bind to BCMA on B cells providing more survival signal to increase basal survival of B cells, and resulting in more production of antibodies (24). Is increase of Nardelli et al reported that sBAFF is produced by enzymatic processing of the membrane-bound protein by conducting experiments with cells transfected with a mutant BAFF cDNA (25), as suggested in Schneider's previous report (26).…”

Section: Discussionmentioning

confidence: 99%

The Abnormal High Expression of B Cell Activating Factor Belonging to TNF Superfamily (BAFF) and Its Potential Role in Kidney Transplant Recipients

Liu

et al. 2008

Cell Mol Immunol

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B cell activating factor belonging to TNF superfamily (BAFF) is a critical regulator of B cell maturation and survival. In this present study, the expression characteristic of BAFF in kidney transplantation recipients was investigated, its potential significance was analyzed and peripheral blood of follow-up kidney transplant recipients was studied. Flow cytometric assay results showed that, cell-surface BAFF was significantly highly expressed on peripheral CD3

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BAFF selectively enhances the survival of plasmablasts generated from human memory B cells

Cited by 78 publications

References 37 publications

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

CNS viral infection diverts homing of antibody‐secreting cells from lymphoid organs to the CNS

The Abnormal High Expression of B Cell Activating Factor Belonging to TNF Superfamily (BAFF) and Its Potential Role in Kidney Transplant Recipients

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