BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact

We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells were not, although both were more resistant than naïve cells. There was also heterogeneity within B1 pools, as splenic but not peritoneal B1 cells were diminished by anti-BLyS treatment, yet the number of natural antibody-secreting cells remained constant. Together, these findings show that memory B cells and natural antibody-secreting cells are BLyS-independent and suggest that these pools can be separately manipulated.     

Recent thymic emigrants,T regulatory cells,and BAFF level in children with X-linked agammaglobulinaemia in association with chronic respiratory disease

Background

X-linked agammaglobulinaemia (XLA) is a genetic disorder affecting B cell maturation, which is characterised by a low number of B cells, agammaglobulinaemia and increased susceptibility to a variety of bacterial infections. This study was performed to assess T cell subpopulations in a group of children with XLA in association with chronic respiratory disease (CRD).

BAFF is elevated in serum of patients with Wegener's granulomatosis

BAFF (B-cell activating factor of the TNF family) plays a crucial role in B-cell survival. Elevated BAFF serum levels have been linked to several autoimmune diseases in humans, and therapies targeting BAFF were successful in animal models of rheumatoid arthritis and systemic lupus erythematosus. Wagener's granulomatosis (WG), a chronic systemic vasculitis, is characterized by circulating autoantibodies (cANCA) targeting neutrophils, which can produce BAFF. To investigate whether BAFF is involved in WG pathology, BAFF serum levels were measured by ELISA in 46 WG patients and 62 healthy donors. We report the novel finding that in WG patients serum levels of BAFF were significantly increased (median 3.95 ng/ml, p=0.009) compared to healthy controls (median 2.38 ng/ml). The difference was even more pronounced when comparing controls with untreated WG patients (median 4.61 ng/ml, p=0.001). Treatment of WG patients with glucocorticoids was associated with lower BAFF levels. The serum BAFF level in treated WG patients was about the same as in the control group. We propose that BAFF might be a pathogenic factor in WG and that targeting BAFF may represent a new therapeutic strategy in a subset of chronically relapsing WG patients with elevated BAFF levels.     

BAFF启动子-871C／T基因多态性在ITP患者中的意义

本研究通过检测B细胞活化因子（BAFF）启动子-871C／T基因多态性在特发性血小板减少性紫癜（ITP）患者中的分布情况,探讨其与ITP发病的相关性,并研究ITP患者初诊时血小板计数与BAFF-871C／T基因型的关系。选择133例ITP患者和117例健康对照者,应用等位基因特异性PcR（ASP—PCR）及琼脂糖凝胶电泳检测BAFF．871C／T多态性。判定各研究对象的基因型,并统计各基因型及等位基因的频率。结果表明：C／C、C／T、T／T3种基因型分布在ITP组分别为33．1％、42．1％、24．8％,对照组分剐为55．6％、33．3％、11．1％。T等位基因频率在111P组为45．9％、对照组为27．4％,差异均有统计学意义（P〈0．05）。ITP组T等位基因频率高于对照组。各基因型间血小板计数无统计学差异（P〉0．05）。结论：BAFF启动子-871C／T多态性可能与111P的发病有相关性,但各基因型之间患者初诊时血小板计数没有差别,不能作为病情严重程度的评价指标。     

Emerging novel treatments for autoimmune liver diseases

The etiology of autoimmune liver diseases, such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), still remains largely unknown and no therapeutic agents that are able to “cure” these diseases have been developed. Although corticosteroids for AIH and ursodeoxycholic acid for PBC have been shown to significantly improve liver transplantation (LT)‐free survival and are recommended as first‐line drugs, treatment strategies for patients who show incomplete response to these drugs have not yet been fully established. No drug is significantly associated with long LT‐free survival in PSC patients. Nevertheless, with progress in genetics, immunology, and cellular biology, several new compounds or antibodies are expected to have an effect on autoimmune liver diseases and several drugs are under consideration for clinical use. Although most clinical trials have been carried out in the USA or Europe, some are, or will be, undertaken in Japan in the future. In this review, the current standard‐of‐care of autoimmune liver diseases will be summarized, together with emerging novel treatments relevant to clinical practice in Japan.     

BAFF is up-regulated in central nervous system of neuro-Behçet's disease

We report that B cell-activating factor of the tumor necrosis factor family (BAFF) is expressed in central nervous system (CNS) of neuro-Beh?et's disease (NBD). This study investigated BAFF and BAFF-R (BAFF receptor) in NBD, compared to multiple sclerosis (MS) and to non inflammatory neurological diseases (NIND). Cerebrospinal fluid (CSF) was used to determine the level of BAFF messenger RNA (mRNA) and the level of BAFF-R mRNA in unfractionated cells. A sandwich ELISA was used to quantify soluble BAFF protein levels in serum and in CSF. BAFF and BAFF-R expression in CSF were increased in NBD and MS patients compared to NIND patients. RNA levels of BAFF and BAFF-R were significantly correlated in NBD and MS patients. Serum sBAFF levels were increased in NBD and MS patients, but did not correlate with BAFF expression in CSF. CNS-produced BAFF may support inflammatory cell survival in NBD.     

Characterisation and expression analysis of B-cell activating factor (BAFF) in spiny dogfish (Squalus acanthias): cartilaginous fish BAFF has a unique extra exon that may impact receptor binding

B-cell activating factor (BAFF), also known as tumour necrosis factor (TNF) ligand superfamily member 13B, is an important immune regulator with critical roles in B-cell survival, proliferation, differentiation and immunoglobulin secretion. A BAFF gene has been cloned from spiny dogfish (Squalus acanthias) and its expression studied. The dogfish BAFF encodes for an anchored type-II transmembrane protein of 288 aa with a putative furin protease cleavage site and TNF family signature as seen in BAFFs from other species. The identity of dogfish BAFF has also been confirmed by conserved cysteine residues, and phylogenetic tree analysis. The dogfish BAFF gene has an extra exon not seen in teleost fish, birds and mammals that encodes for 29 aa and may impact on receptor binding. The dogfish BAFF is highly expressed in immune tissues, such as spleen, and is up-regulated by PWM in peripheral blood leucocytes, suggesting a potentially important role in the immune system.