Bursa of Fabricius

Aflatoxin B₁ (AFB₁) is a serious threat to the poultry industry. Proanthocyanidins (PCs) demonstrates a broad range of biological, pharmacological, therapeutic, and chemoprotective properties. The aim of this study was to investigate the ameliorative effects of PCs against AFB₁-induced histopathology, oxidative stress, and apoptosis via the mitochondrial pathway in the bursa of Fabricius (BF) of broilers. One hundred forty-four one-day old Cobb chicks were randomly assigned into four treatment groups of six replicates (6 birds each replicate) for 28 days. Groups were fed on the following four diets; (1) Basal diet without addition of PCs or AFB₁ (Control); (2) basal diet supplemented with 1 mg/kg AFB₁ from contaminated corn (AFB₁); (3) basal diet supplemented with 250 mg/kg PCs (PCs); and (4) basal diet supplemented with 1 mg/kg AFB₁ + 250 mg/kg PCs (AFB₁+ PCs). The present study results showed that antioxidant enzymes activities of total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione S-transferase (GST) in AFB₁ treated group were (p SOD, CAT, GPx1, and GST) in comparison with AFB₁ group. Moreover, histological results showed that PCs alleviated AFB₁-induced apoptotic cells in the BF of broilers. In addition, both mRNA and protein expression results manifested that mitochondrial-apoptosis-associated genes (Bax, caspase-9, caspase-3, and p53 and cytochrome c) showed up-regulation, while (Bcl-2) showed down-regulation in AFB₁ fed group. The supplementation of PCs to AFB₁ diet significantly reversed the mRNA and protein expression of these apoptosis-associated genes, as compared to the AFB₁ group. Our results demonstrated that PCs ameliorated AFB₁-induced oxidative stress by modulating the antioxidant defense system and apoptosis in the BF through mitochondrial pathway in broilers.

Aflatoxin B1 (AFB1), a toxic metabolite produced by some fungi, exerts well-known hepatocarcinogenic and immunosuppressive effects, the latter can increase the apoptotic immune cells in vitro. However, it is largely unknown that which signaling pathways contribute to excessive apoptosis of immune cells which induced by AFB1. In this study, we investigated the roles of the mitochondria, endoplasmic reticulum (ER) and death receptor activated apoptotic pathways in the bursal of Fabricius (BF) cells in the broilers exposed to AFB1 diet. We found that (1) AFB1 diet induced morphological changes in the BF. (2) FCM and TUNEL methods showed that excessive apoptosis could be resulted from AFB1 intake. (3) AFB1-induced apoptosis of bursal cells involved mitochondrial pathway (increase of Bax, Bak, cytC, caspase-9, Apaf-1, caspase-3 and decrease of Bcl-2 and Bcl-xL) and ER pathway (increase of Grp78/Bip, Grp94 and CaM). (4) Oxidative stress was confirmed in the BF of chicken fed on AFB1 diet. Overall, this work is the first to demonstrate that the activation of mitochondria and ER apoptosis pathways can lead to excessive apoptosis in BF cells, and oxidative stress is a crucial driver during AFB1 exposure.

The bursa of Fabricius is a primary and secondary lymphoid organ considered exclusively present in birds, and studies of this structure have been vital to our current understanding of the adaptive immune system of vertebrates. In this study, we reveal substantial lymphoepithelial tissue in a previously undescribed bursa in Atlantic salmon (Salmo salar), situated caudal to the urogenital papilla of the cloaca and thus analogous to the anatomical placement of the bursa of Fabricius. We investigated three groups of Atlantic salmon at different maturational stages and characterized the structure by applying dissection, radiology, scanning electron microscopy and histological techniques, including immunohistochemistry and in situ hybridization. We found that the epithelial anlage of the salmon cloacal bursa developed into substantial lymphoepithelial tissue and subsequently regressed following sexual maturation. Such a dynamic development is also a key characteristic of the avian bursa. The presence of intraepithelial lymphocytes was concomitant with expression of the leukocyte-attracting chemokine CCL19, indicative of lymphoid organ functions. We did not observe recombination or gene conversion in salmon bursal lymphocytes at any developmental stage, indicating the absence of primary lymphoid organ functions in contrast to the bursa of Fabricius. However, the possibility of the bursa to trap both enteric and environmental antigens, combined with the presence of several antigen-presenting cells residing within the lymphoepithelium, suggest the structure has secondary lymphoid organ functions. We present the discovery of a lymphoid organ in Atlantic salmon with striking topographical similarities to that of the bursa of Fabricius in birds. In addition, the age-dependent dynamics of its lymphoepithelium suggest functions related to the maturation processes of lymphocytes.

The bursa of Fabricius (BF), a specialized lymphoid structure in birds, regulates avian B-cell development. However, the BF starts to regress posthatching, suggesting that as-yet-unidentified structures assume this function during maturation. This study reveals that BF-independent B-cell genesis involving the gut cecal tonsils (CTs) predominates over the BF-dependent pathway posthatching. Although B-cell progenitors originating from the bone marrow (BM) typically migrate to the BF, we identified a population that instead migrates to the CTs through CXCL12/CXCR4-mediated chemotaxis. These BF-independent CXCR4+ pre-B cells acquired surface IgM expression within the CT follicular region (FR) and differentiated into immunoglobulin A (IgA)-producing plasma cells. Inhibition of CXCR4+ cell influx from the BM impaired formation of the FR, altered the responsiveness of intestinal IgA to commensal bacteria, promoted gut dysbiosis, allowed translocation of pathogenic bacteria (e.g., Streptococcus alactolyticus) to the liver, and ultimately caused hepatic inflammation and metabolic dysfunction. These abnormalities were reversed by administering an IgA-enriched fecal preparation derived from healthy chickens. Collectively, these results reveal the existence of a population of BF-independent B cells that function in CTs. These cells represent a promising target for maintaining and improving the immunological and microbiological environment of the avian intestinal tract, which is closely linked to hepatic homeostasis.