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The chick immune system is a fundamental model in basic immunology. In birds, the bone marrow derived pluripotent stem cells after entering the circulation, migrate to bursa of Fabricius to benefit from a microenvironment which supports the differentiation and maturation of B lymphocytes by the help of its resident cells and tissues. Delivering sufficient functional B cells is required to maintain their peripheral population and normal peripheral humoral responses. Additionally, bursa acts as an active site for the generation of antibody diversity through gene conversion. Being consisted of 98% B lymphocytes, the organ is occupied by other cell types including T cells, macrophages, eosinophils and mast cells. Thymus, which is an epithelial organ is the main site of T cell development where positive and negative selections contribute to the development of functional and not autoreactive T cell repertoire. Bursectomy and thymectomy are surgical exercises through which the involvement of cells of specific immunity including B cells and T cells can be determined., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Infectious bursal disease virus (IBDV) is a very important small RNA virus in the family of Birnaviridae, which can cause severe immunosuppressive effects and pathological damages in young chickens. It can replicate in bursal lymphocytes and impede the growth and development of B cells, finally causing bursal lymphocytes apoptosis. Previous results have shown that protocatechuic acid (PCA) as an important phenolic compound could effectively improve the survival rate of chickens infected with IBDV. The current study aimed to explore how PCA influenced the pathogenesis of IBDV, especially lymphocyte apoptosis in the process of IBDV infection. The results showed that PCA could effectively alleviate bursal pathological changes at the early stage of IBDV invasion. Moreover, bursal lymphocyte apoptosis for tissue section samples was largely elevated by PCA by using the terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method while the bursal lymphocyte apoptosis ratio was also increased by PCA by flow cytometry in the early stage of IBDV infection in vivo. Meanwhile, PCA could promote non-lymphocyte apoptosis in vitro. Further study displayed that the potential mechanisms mainly relied on regulation of the expressions of pro-apoptotic protein Bax and anti-apoptotic Bcl-2, thus speeding up the process of IBDV-infected cell apoptosis and preventing virus infection. Meanwhile, the results displayed that the PI3K/Akt and NF kappa B signal pathways might play an important role in promoting cell apoptosis after IBDV infection. Overall, PCA as a potent antiviral drug precursor is expected to be applied in the poultry industry as a substitute for clinical antiviral application., (Copyright © 2018. Published by Elsevier Ltd.)

Toll like receptor 4 (TLR4), eosinophils and mast cells play significant role in host immunity during several pathogenic infections. However in vivo tissue expression of TLR4 and distribution pattern of eosinophils and mast cells in chicken bursa of Fabricius (BF) during Salmonella enterica serovar Typhimurium (STm) infection is poorly studied. Therefore, herein, following immunostaining, we found localization of TLR4 in follicular cortex and medulla and its expression was statistical increased after 36 h and 72 h of STm stimulation. Chromotrope 2R staining revealed that eosinophils were mostly distributed in follicular cortex, inter-follicular spaces and in or around blood vessels and their number in BF were statistical increased after 72 h of STm stimulation. The presence of eosinophils was confirmed using immunostaining with anti-rabbit eosinophil cationic protein antibody. Toluidine blue stained mast cells were mostly distributed in connective tissues between inter-follicular spaces while some were also present in follicular cortex of BF. However, STm stimulation illustrated non-significant effect on the number of mast cells or their de-granulation, instead their number were gradually decreased in BF with advancement in age of chickens. Hence, this study provided novel information about in vivo tissue distribution of TLR4, eosinophils and mast cells in BF during STm infection., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Growth hormone (GH) is expressed in several extra-pituitary tissues, including the primary and secondary lymphoid organs of the immune system. In birds, GH mRNA and protein expression show a specific developmental distribution pattern in the bursa of Fabricius (BF), particularly in epithelial and B cells. Changes in the bursal concentration and distribution of locally produced GH during ontogeny suggest it is involved in B cell differentiation and maturation, as well as in a functional survival role in this organ, which may be mediated by paracrine/autocrine mechanisms. Here, we analyzed the anti-apoptotic effect of GH in BF and the intracellular signaling pathways involved in this activity. Also, we studied if this effect was exerted directly by GH or mediated indirectly by IGF-I. Bursal cell cultures showed an important loss of their viability after 4h of incubation and a significant increase in apoptosis. However, treatment with 10nM GH or 40 nM IGF-I significantly increased B cell viability (16.7 ± 0.67% and 13.4 ± 1.12%, respectively) when compared with the untreated controls. In addition, the presence of apoptotic bodies (TUNEL) dramatically decreased (5.5-fold) after GH and IGF-I treatments, whereas co-incubation with anti-GH or anti-IGF-I, respectively, blocked their anti-apoptotic effect. Likewise, both GH and IGF-I significantly inhibited caspase-3 activity (by 40 ± 2.0%) in these cultures. However, the use of anti-IGF-I could not reverse the GH anti-apoptotic effects, thus indicating that these were exerted directly. The addition of 100 nM wortmannin (a PI3K/Akt inhibitor) blocked the GH protective effects. Also, GH stimulated (3-fold) the phosphorylation of Akt in bursal cells, and adding wortmannin or an anti-GH antibody inhibited this effect. Furthermore, GH was capable to stimulate (7-fold) the expression of Bcl-2. Taken together, these results indicate that the direct anti-apoptotic activity of GH observed in the chicken bursal B cell cultures might be mediated through the PI3K/Akt pathway., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Growth hormone (GH) is expressed in the chicken bursa of Fabricius (BF), an organ that undergoes three distinct developmental stages: rapid growth (late embryogenesis until 6-8 weeks of age [w]), plateaued growth (between 10 and 15w), and involution (after 18-20w). The distribution and abundance of GH-immunoreactivity (GH-IR) and GH mRNA expression in stromal and non-stromal bursal cells during development, as well as the potential anti-apoptotic effect of GH in bursal cell survival were the focus of this study. GH mRNA expression was mainly in the epithelial layer and in epithelial buds at embryonic day (ED) 15; at 2w it was widely distributed within the follicle and in the interfollicular epithelium (IFE); at 10w it clearly diminished in the epithelium; whereas at 20w it occurred in only a few cortical cells and in the connective tissue. Parallel changes in the relative proportion of GH mRNA expression (12, 21, 13, 1%) and GH-IR (19, 18, 11, <3%) were observed at ED 15, 2w, 10w, and 20w, respectively. During embryogenesis, GH-IR co-localized considerably with IgM-IR, but scarcely with IgG-IR, whereas the opposite was observed after hatching. Significant differences in bursal cell death occurred during development, with 9.3% of cells being apoptotic at ED 15, 0.4% at 2w, 0.23% at 10w, and 21.1% at 20w. Addition of GH increased cultured cell survival by a mechanism that involved suppression (up to 41%) of caspase-3 activity. Results suggest that autocrine/paracrine actions of bursal GH are involved in the differentiation and proliferation of B lymphocytes and in BF growth and cell survival in embryonic and neonatal chicks, whereas diminished GH expression in adults may result in bursal involution., (Copyright 2010 Elsevier Inc. All rights reserved.)

The bursa of Fabricius provides a unique organ for the study of lineage-specific development in a multicellular organism. Unlike mammalian B cells, B cells in the chicken develop in a single wave of differentiation, beginning with the commitment of progenitor cells to the B cell lineage between days 10 and 15 of embryogenesis. By day 18 of embryogenesis, all lymphoid progenitor cells capable of differentiation along the B cell lineage have migrated to the bursa of Fabricius. Following migration to the bursa, these lymphoid progenitors enter exponential growth and begin to populate each of the 10(4) bursal follicles. Between day 18 of embryogenesis and 2-4 weeks of age, B cells undergo a stage of bursal-dependent differentiation. By the end of this period, chickens are able to mount primary immune responses against virtually all antigens. In addition, by this time sufficient numbers of B cells have migrated from the bursa to peripheral lymphoid organs so that the B cell immune system can be maintained even if the bird is bursectomized. Bursectomy of chicks after 4 weeks of age has no long-term effects on the development and maintenance of the B cell immune system in adult birds. Because of the central nature of the surface Ig molecule to B cell development in mammals, the chicken IgL gene locus has been intensively studied during avian B cell development. The chicken IgL locus is a particular interest because it has only one V region capable of rearrangement. Rearrangement of the IgL gene is not dependent on the bursal environment. B cell progenitors rearrange their IgL gene between days 10-15 of embryogenesis, prior to migration to the bursa. IgL gene rearrangement occurs by a deletional mechanism in which a precise joining of the IgL recombination signal sequences leads to a circular episomal element. During this deletion it appears that single nonrandom bases are added to both the V and J coding segments. Subsequent V-J joining occurs at random. Most progenitor B cells appear to rearrange only a single IgL allele. The high frequency of in-frame alleles observed in avian B cell lines appears to result from the selective amplification of cells with productive IgL rearrangements during bursal development between days 12 and 18 of embryogenesis. To create an immunological repertoire, chickens must diversify the coding sequence of this single functional V gene segment during development.(ABSTRACT TRUNCATED AT 400 WORDS)

Sex steroids were found to affect both murine and avian immune systems. Female and male (NZB X NZW)F1 mice were castrated at 2 weeks of age and given Silastic implants containing either dihydrotestosterone or estradiol. Four weeks following treatment, the thymuses were studied for cell cycle kinetics and for the presence of various cell surface antigens using fluorescein-conjugated antisera and flow cytometric techniques. Estradiol therapy resulted in an increase in mature thymocytes, that is, thymocytes that had decreased peanut agglutinin receptors and decreased Thy 1 antigens on their surfaces. Additional studies with anti-Lyt 1 and 2 indicated that these mature thymocytes were of the "helper" rather than the "suppressor" phenotype. Estradiol therapy resulted in an increase in the percentages of proliferating cells in the spleen and a decrease in the percentages of proliferating cells in the thymus. In contrast, in the avian system, estradiol had little effect on proliferation in immunological organs. Dihydrotestosterone was a potent inhibitor of proliferation in the avian bursa. These results indicate that sex hormones have specific effects on different immune cell subpopulations. In the murine system the male is the heterogametic sex but in the avian system the female is the heterogametic sex. Based upon the present and previous studies, we suggest that the primary modulating hormone for immunological sex effects in the mammal is estrogen, whereas in the bird it is androgen.

The effect of ovine prolactin (NIH-LTH) in different does (1.5, 5.0, 10.0 IU) on the mitotic activity of the bursa of Fabricius of the chick was studied. Prolactin at all doses increased the mitotic activity, but the lowest dosage (1.5 IU) was most effective). Also, prolactin, at all doses, inhibited histologically bursal secretory activity. Thus, dual action of prolactin on bursal activity in chicks is indicated.

Chickens were surgically bursectomized at 60 hr of incubation, before the bursal anlage appears. Completeness of the bursectomy was confirmed at autopsy at 10 weeks of age. These embryonically bursectomized (Bx)3 chickens are known to produce immunoglobulins of IgM, IgG, and IgA classes but so far no specific antibodies have been observed even after heavy immunization. The Bx chickens had mature plasma cells in an almost normal frequency when studied at 10 weeks of age. The amount of germinal center formation in the spleen and cecal tonsils was markedly decreased when compared to the control (Co) chickens. Also, the frequency of cytoplasmic IgA-positive (c-IgA+) cells was severely decreased in the Bx animals, whereas the occurrence of c-IgG+ and c-IgM+ cells was not affected to the same extent. These findings support the hypothesis that heavy-chain class switch may occur without the bursal influence, and that the bursa of Fabricius is essential only for expansion or creation of the antibody repertoire.

University of California, Davis (UCD) line 140 chickens develop a dysgammaglobulinemia characterized as selective 7S immunoglobulin (Ig) deficiency with elevated serum IgM levels. To study the role of bursal development on the expression of dysgammaglobulinemia in these birds, we examined the effect of bursacyte transfer to line 140 birds and parabiosis between UCD 140 and a control line of chickens on changes in serum IgM and 7S Ig levels. Bursacyte transfer was performed by injecting 18-day UCD 140 embryos (which had been cyclophosphamide treated on Day 15) with bursacytes from major histocompatibility complex B-matched control line (11 X 58) F1 birds. This transfer produced little change in the incidence of dysgammaglobulinemia in UCD 140 transfer birds (56%) compared to unmanipulated line 140 birds (60%). These data reflect a failure of line 140, rather than technique, because successful reconstitution was seen using line 11 X 58 birds injected with 11 X 58 bursacytes. In contrast, the generation of UCD 140/line 11 X 58 chimeras significantly reduced the incidence of dysgammaglobulinemia in line UCD birds. Indeed, fusion of the chorioallantoic vascular system (parabiosis) of UCD 140 and 11 X 58 embryos on Day 15 decreased the frequency of dysgammaglobulinemia of UCD 140 parabionts to 14% compared to 66% in unmanipulated line 140 controls. The success of parabiosis was 83% as determined by demonstrating chimerism with allogeneic blood groups. Moreover, the frequency of dysgammaglobulinemia in the 17% of parabionts that did not reveal chimerism was similar to unmanipulated UCD 140 chickens.