The mucosae and exocrine glands harbour the largest activated B-cell system of the body, amounting to some 80-90% of all immunoglobulin (Ig)-producing cells. The major product of these immunocytes is polymeric (p)IgA (mainly dimers) with associated J chain. Both pIgA and pentameric IgM contain a binding site for the polymeric Ig receptor (pIgR), or secretory component (SC), which is a requirement for their active external transport through secretory epithelia. The pIgR/SC binding site depends on covalent incorporation of the J chain into the quaternary structure of the polymers when they are produced by the local immunocytes. This important differentiation characteristic appears to be sufficient functional justification for the J chain to be expressed also by most B cells terminating at secretory effector sites with IgD or IgG production; they probably represent a "spin-off" from sequential downstream CH switching on its way to pIgA expression, thus apparently reflecting a maturational stage of effector B-cell clones compatible with homing to these sites. Observations in IgA-deficient individuals suggest that the magnitude of this homing is fairly well maintained even when the differentiation pathway to IgA is blocked. Certain microenvironmental elements such as specific cytokines and dendritic cells appear to be required for induction of IgA synthesis, but it remains virtually unknown why this isotype normally is such a dominating product of local immunocytes and why they have such a high level of J chain expression. Also, despite the recent identification of some important requirements in terms of adhesion molecules (e.g. integrin alpha 4 beta 7 and MAdCAM-1) that explain the "gut-seeking" properties of enterically induced B cells, the origin of regionalized homing of B cells to secretory effector sites outside the gut remains elusive. Moreover, little is known about immune regulation underlying the striking disparity of both the class (IgD, IgM) and subclass (IgA1, IgA2, IgG1, IgG2) production patterns shown by local immunocytes in various regions of the body, although the topical microbiota and other environmental stimuli might be important. Rational design of local vaccines will depend on better knowledge of both inductive and migratory properties of human mucosal B cells.

Norwegian aquaculture has grown from its pioneering days in the 1970s to be a major industry. It is primarily based on culturing Atlantic salmon and rainbow trout and has the potential to influence the surrounding environment and wild populations. To evaluate these potential hazards, the Institute of Marine Research initiated a risk assessment of Norwegian salmon farming in 2011. This assessment has been repeated annually since. Here, we describe the background, methods and limitations of the risk assessment for the following hazards: genetic introgression of farmed salmon in wild populations, regulatory effects of salmon lice and viral diseases on wild salmonid populations, local and regional impact of nutrients and organic load. The main findings are as follows: (i) 21 of the 34 wild salmon populations investigated indicated moderate-to-high risk for genetic introgression from farmed escaped salmon. (ii) of 109 stations investigated along the Norwegian coast for salmon lice infection, 27 indicated moderate-to-high likelihood of mortality for salmon smolts while 67 stations indicated moderate-to-high mortality of wild sea trout. (iii) Viral disease outbreaks (pancreas disease, infectious pancreatic necrosis, heart and skeletal muscle inflammation, and cardiomyopathy syndrome) in Norwegian salmon farming suggest extensive release of viruses in many areas. However, screening of wild salmonids revealed low to very low prevalence of the causal viruses. (iv) From ∼500 yearly investigations of local organic loading under fish farms, only 2% of them displayed unacceptable conditions in 2013. The risk of eutrophication and organic load beyond the production area of the farm is considered low. Despite several limitations, especially limited monitoring data, this work represents one of the world’s first risk assessment of aquaculture. This has provided the Norwegian government with the basis upon which to take decisions for further development of the Norwegian aquaculture industry.

IntroductionRheumatoid arthritis (RA) and ulcerative colitis (UC) are chronic inflammatory diseases associated with de novo formation of irregular T-and B-cell aggregates in the synovium 1 and large bowel mucosa, 2 respectively. Such local development of lymphoid tissue is thought to contribute to the pathology of chronic inflammation. 3,4 Lymphoid tissue organization is orchestrated by a subset of the chemokine family, termed homeostatic or lymphoid chemokines because of their constitutive expression in secondary lymphoid tissues. 5 One of these lymphoid chemokines, CXCL13, also called B cell-attracting chemokine 1 (BCA-1) 6 or B-lymphocyte chemoattractant (BLC), 7 and its receptor CXCR5, also called Burkitt lymphoma receptor-1 (BLR1), are required for normal development of secondary lymphoid organs in mice. 8,9 CXCL13 and CXCR5 have, in addition, been detected in various chronic human inflammatory diseases where lymphoid neogenesis occurs, such as Helicobacter pylori gastritis, 10 RA, 1,11 Sjögren syndrome, 12-14 and UC 15 as well as in gastric 10 and primary central nervous system lymphoma. 16 Follicular dendritic cells (FDCs) are generally believed to be the main source of CXCL13 in normal 6,7,17 as well as inflamed lymphoid tissue. 1,10,11 In addition, vascular expression of the CXCL13 protein has been reported, 1,15,16,18,19 and CXCL13 and CXCR5 have been shown to play an important role in B-cell homing to murine Peyer patches. 20 However, no expression analysis of CXCL13 mRNA in human lymphoid tissue 10,15,16,18 has directly shown that CXCL13 is actually produced by FDCs or endothelial cells. Importantly, available data do not exclude the possibility that murine FDCs in fact bind CXCL13 rather than produce it. 7,17 Also of note, CXCL13 protein is undetectable in human FDC-like cells stimulated in vitro. 21 We have shown earlier that another lymphoid chemokine, CCL19, is present and functions in endothelial cells that are not its source. 22 In our recent human study of normal and aberrant gutassociated lymphoid tissue, we found that CXCL13 was mainly associated with extracellular fibrils and only minimally with cells displaying the traditional FDC phenotype. 15 This prompted us to explore more extensively the source of this chemokine in human lymphoid neogenesis represented by RA synovium and UC large bowel mucosa. Furthermore, we investigated the potential mechanistic role monocyte-derived cells could play in CXCL13 secretion. Our data documented for the first time that human monocytes/ macrophages are a potent inducible source of CXCL13 and, in fact, appear to be the main producers of this chemokine in inflammatory lesions where lymphoid neogenesis occurs. This suggested a role of recently extravasated macrophages in the formation of such ectopic follicles. Patients, materials, and methods PatientsClinicopathologic data and patient treatment schedules are provided in Table 1. Cryosections (8 m) were cut serially from various human tissue For personal use only. on May 10, 2018. by guest www.bloodjournal.o...

Both IgG and IgA Abs have been implicated in host defense against bacterial infections, although their relative contributions remain unclear. We generated a unique panel of human chimeric Abs of all human IgG and IgA subclasses with identical V genes against porin A, a major subcapsular protein Ag of Neisseria meningitidis and a vaccine candidate. Chimeric Abs were produced in baby hamster kidney cells, and IgA-producing clones were cotransfected with human J chain and/or human secretory component. Although IgG (isotypes IgG1–3) mediated efficient complement-dependent lysis, IgA was unable to. However, IgA proved equally active to IgG in stimulating polymorphonuclear leukocyte respiratory burst. Remarkably, although porin-specific monomeric, dimeric, and polymeric IgA triggered efficient phagocytosis, secretory IgA did not. These studies reveal unique and nonoverlapping roles for IgG and IgA Abs in defense against meningococcal infections.