Granja Aitor G, Holland Jason W, Pignatelli Jaime, Secombes Christopher J, Tafalla Carolina
Centro de Investigación en Sanidad Animal (CISA-INIA). Valdeolmos (Madrid), Spain.
Scottish Fish Immunology Research Centre, University of Aberdeen, Aberdeen, United Kingdom.
PLoS One. 2017 Mar 21;12(3):e0174249. doi: 10.1371/journal.pone.0174249. eCollection 2017.
Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish characterized by hyper-secretion of immunoglobulins in response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In this context, we hypothesized that the BAFF/APRIL axis, known to play a major role in B cell differentiation and survival in mammals, could be affected by the parasite and consequently be involved in the apparent shift in normal B cell activity. To regulate B cell activity, BAFF and APRIL bind to transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), whereas BAFF also binds to BAFF receptor (BAFF-R). In teleost fish, although some BAFF and APRIL sequences have been reported, their receptors have not been identified. Thus, as a first step in the current work, we have identified homologues to mammalian TACI, BCMA and BAFF-R in rainbow trout (Oncorhynchus mykiss), that constitute the first report of BAFF and APRIL receptor sequences in fish. Subsequently we studied the transcriptional modulation of BAFF, APRIL, and the fish-specific related cytokine, BALM and their putative receptors in fish naturally exposed to T. bryosalmonae. Finally, to gain further insights on the functional role that these cytokines play during the course of PKD, we have studied their effect on the survival of kidney IgM+ B cells and on immunoglobulin transcription. Our results support the premise that the BAFF / APRIL axis could play an important role during PKD, which may open the possibility of new therapeutic treatments against the disease.
增殖性肾病（PKD）是鲑科鱼类的一种寄生虫感染疾病，其特征是在粘孢子虫寄生虫——脑粘体虫（Tetracapsuloides bryosalmonae）存在的情况下免疫球蛋白过度分泌。在此背景下，我们推测，已知在哺乳动物B细胞分化和存活中起主要作用的BAFF/APRIL轴可能受到该寄生虫的影响，从而参与正常B细胞活性的明显变化。为调节B细胞活性，BAFF和APRIL与跨膜激活剂、钙调节剂和亲环素配体相互作用分子（TACI）以及B细胞成熟抗原（BCMA）结合，而BAFF还与BAFF受体（BAFF-R）结合。在硬骨鱼中，虽然已经报道了一些BAFF和APRIL序列，但它们的受体尚未确定。因此，作为当前工作的第一步，我们在虹鳟（Oncorhynchus mykiss）中鉴定出了与哺乳动物TACI、BCMA和BAFF-R的同源物，这是鱼类中BAFF和APRIL受体序列的首次报道。随后，我们研究了自然暴露于脑粘体虫的鱼类中BAFF、APRIL以及鱼类特异性相关细胞因子BALM及其假定受体的转录调控。最后，为了进一步深入了解这些细胞因子在PKD病程中发挥的功能作用，我们研究了它们对肾IgM+B细胞存活和免疫球蛋白转录的影响。我们的结果支持这样一个前提，即BAFF/APRIL轴可能在PKD期间发挥重要作用，这可能为针对该疾病的新治疗方法开辟可能性。
