• 대한수의학회지
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• 제1권1호
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• pp.54-60
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• 1961

For the purpose of investigating seasonal changes of germinal centers of splenic lymph nodules and of blood lymphocytes of ducks, the spleens of 8 ducks from a flock were observed histologically every season; 2 cases in spring (March and April), 2 in summer (July and August), 2 in autumn (October and November) and 2 in winter (December and January). Blood cells of 8 ducks from the same flock also were counted during the summer (from July to August) and autumn (from October to November) The results obtained were summarized as follows: 1. There were seasonal changes in the germinal centers of lymph nodules, that is, the germinal centers were formed in spring and disappeared in autumn. In summer these were at the stage of transition from formation in spring to disappearance in autumn. In winter, on tile other hand. the process was reversed from the stage of disappearance in autumn to the stage of formation in spring. 2. The germinal center of splenic lymph nodule was encapsulated with a fibrous capsule which disappeared concommitantly with its germinal center. 3. The percentage and absolute value of lymphocytes in autumn were higher than those in summer, the fact that seemed to be not in agreement with Flemming's view that the lymphocytic clear germinal center may be functionally at the stage of lymphocyte formation, but in agreement with Maximow's view that the large lymphocytic clear germinal center is functionally at the stage of resting and medium-sized lymphocytic germinal center may be functionally at the stage of lympocyte formatiom.

• Animal cells and systems
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• 제12권3호
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• pp.127-136
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• 2008

Caspase-11 has been known as a dual regulator of cytokine maturation and apoptosis. Although the role of caspase-11 under pathological conditions has been well documented, its physiological role has not been studied much. In the present study, we investigated a possible physiological function of caspase-11 during immune response. In the absence of caspase-11, immunized spleen displayed increased cellularity and abnormal germinal center structure with disrupted microarchitecture. The rate of cell proliferation and apoptosis in the immunized spleen was not changed in the caspase-11-deficient mice. Furthermore, the caspase-11-deficient peritoneal macrophages showed normal phagocytotic activity. However, caspase-11-/-splenocytes and macrophages showed defective migrating capacity. The dysregulation of cell migration did not seem to be mediated by caspase-3, interleukin-$1{\alpha}$ or interleukin-$1{\beta}$ which acts downstream of caspase-11. These results suggest that a direct regulation of immune cell migration by caspase-11 is critical for the formation of germinal center microarchitecture during immune response. However, humoral immunity in the caspase-11-deficient mice was normal, suggesting the formation of germinal center structure is not essential for the affinity maturation of the antibodies.

• BMB Reports
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• 제29권2호
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• pp.127-132
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• 1996

Germinal centers (GCs) are formed in peripheral lymphoid tissues in response to protein antigens. In order to see if immunoglobulin isotype switching takes place in GC B-cells, we isolated GC B-cells (PNA positive cells) from mouse popliteal lymph nodes by a flow cytometer after the staining of lymph node cells with PNA-FITC and anti-B220-PE, and determined the expression of ${\gamma}1$ germline transcript and ${\gamma}1$ mRNA by RT-PCR. ${\gamma}1$ germline transcript and ${\gamma}1$ mRNA were amplified specifically in cDNAs from hybridoma expressing IgG1 or splenocytes stimulated LPS plus IL-4. Germinal center B-cells formed in popliteal lymph nodes of mice immunized with chicken ovalbumin were isolated 7 days after immunization. We sorted GC B-cells five times. Immunoglobulin ${\gamma}1$ germline transcripts were expressed in germinal center B-cells in three out of five sorts whereas two out of five sorts did not express ${\gamma}1$ germline transcripts in GC B-cells. The contents of GC B-cells ranged from 5 to 7% of total lymph node cells in most flow cytometric analyses but those of two sorted cells which did not express ${\gamma}1$ germline transcripts were out of normal range. These results imply that isotype switching of immunoglobulins may take place in GCs.

• 한국발생생물학회지:발생과생식
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• 제20권4호
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• pp.359-365
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• 2016

Intact germinal vesicle (GV) arrest and release are essential for maintaining the fertility of mammals inducing human. Intact germinal vesicle release, maturation of oocytes is maintained by very complex procedures along with folliculogenesis and is a critical step for embryonic development. Cyclic guanosine monophosphate (cGMP) has been suggested a key factor for meiotic arrest but so far its mechanisms are controversy. In this study we examine the effects of cGMP on germinal vesicle breakdown in cumulus-enclosed oocytes and denuded oocytes. Spontaneous maturation was inhibited by a cGMP agonist, 8-Br-cGMP with concentration dependent manners both in cumulus-enclosed oocytes and denuded oocytes. The inhibitory effect was more severe in denuded oocytes than cumulus-enclosed oocytes. The Rp-8-Br-cGMP and Rp-pCPT-8-Br-cGMP did not severely block GVB compared to 8-Br-cGMP. The spontaneous GVB inhibitory effects were different by the existence of cumulus. Based on them it is suggested that the cumulus modulates the role of cGMP in GV arrest.

• Clinical and Experimental Reproductive Medicine
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• 제1권1호
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• pp.49-54
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• 1974

In the present studies, effect of progesterone on the germinal vesicle break-down of the mouse oocytes cultured in the micro tube was investigated. The results obtained are as follows: As dose of progesterone in the medium rose, accordingly the break-down of the germinal vesicle was suppressed. It was found that $ED_{50}$ was 15.7 ${\mu}g$/ml, and $ED_{90}$ 60.7 ${\mu}g$/ml of progesterone. The dose suppressing the oocyte maturation was apparently higher than that on the rabbit or on the mouse embryonal development. The inhibiting effect of progesterone on the GVBD was reversible. The germinal vesicle of the oocytes were broken down immediately in the medium upon removal of the hormone. Progesterone stops meiosis at any stage upon administration, while dbe AMP or theophylline supresses only the break-down of the nuclear membrane. Recovering of the meiotic division of the oocytes once exposed to progesterone was delayed a little. The inhibiting action of progesterone was not altered by adding more pyruvate or in the presence of higher concentration of the mineral ions in the culture medium.

• 한양메디칼리뷰
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• 제33권1호
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• pp.10-16
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• 2013

Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORγt. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORγt, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.244-251
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• 2016

Understanding the developmental mechanisms of humoral immunity against intranasal antigens is essential for the development of therapeutic approaches against air-borne pathogens as well as allergen-induced pulmonary inflammation. Follicular helper T (Tfh) cells expressing CXCR5 are required for humoral immunity by providing IL-21 and ICOS costimulation to activated B cells. However, the regulation of Tfh cell responses against intranasal antigens remains unclear. Here, we found that the generation of Tfh cells and germinal center B cells in the bronchial lymph node against intranasal proteinase antigens was independent of $TGF-{\beta}$. In contrast, administration of STAT3 inhibitor STA-21 suppressed the generation of Tfh cells and germinal center B cells. Compared with wild-type OT-II T cells, STAT3-deficient OT-II T cells transferred into recipients lacking T cells not only showed significantly reduced frequency Tfh cells, but also induced diminished IgG as well as IgE specific for the intranasal antigens. Cotransfer study of wild-type OT-II and STAT3-deficient OT-II T cells revealed that the latter failed to differentiate into Tfh cells. These findings demonstrate that T cell-intrinsic STAT3 is required for the generation of Tfh cells to intranasal antigens and that targeting STAT3 might be an effective approach to ameliorate antibody-mediated pathology in the lung.

• 대한두경부종양학회지
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• 제31권1호
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• pp.34-38
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• 2015

Progressive transformation of germinal centers(PTGC) is a rare benign lymph node enlargement characterized by chronic lymphadenopathy and the presence of germinal centers with fused and expanded mantles within a lymph node that are 3-5 times the size of a typical reactive follicle. Although PTGC is reported in 3.5-10% of chronic lymphadenopathy, head and neck surgeons do not often experience this condition and its clinical implications. Althoug PTGC is benign disease, it could not be excluded the association with other malignant lymphoid diseases. Therefore, periodic follow up of PTGC patient could be required. We report two cases at this study ; a 16 years old man who visited out-patient clinic due to palpable mass of right cervical area, several months ago, and a 35 years old man who visited out-patient clinic for evaluating right cervical mass. Both of two patients were diagnosed with PTGC. In this study, we focus on the clinic-pathologic features of this uncommon disease along with other literature reviews.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.61-61
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• 2003

We have investigated the novel function of tissue transglutaminase (tTG) in the germinal vesicle breakdown (GVBD) of mouse oocyte. tTG was identified in ooplasm and germinal vesicle by immunostaining assay. Spontaneous maturation of the oocytes elevated in situ activity of tTG by over 2.5 fold at 3 hr, which was determined by a confocal microscopic assay. However, incubation with monodansylcadaverine (MDC), a tTG inhibitor, blocked the activation of tTG. The possible role of tTG in GVBD was investigated by the use of two tTG inhibitors, MDC and cystamine. MDC largely inhibited the GVBD by a concentration dependent manner. GV-stage oocytes were matured to the GVBD stage by 78% at 3 hr in BWW culture medium. However, in the oocytes incubated with MDC for 3 hr, the GVBD rates were 43 and 11% by 50 and 100 mM, respectively. MDC also blocked the entry of 70 kDa TRITC-dextran from the ooplasm to the compartment of germinal vesicle, indicating a possible inhibition of nuclear pore disassembly by MDC. The role of tTG in GVBD was further investigated by microinjection with cystamine. The control oocytes, injected with DPBS, showed about 80 % of GVBD at 3 hr. But the oocytes injected with cystamine showed 15% of GVBD at 3 hr and a little higher rate at 6 hr. In addition, the inhibition of GVBD maturation by MDC was reversible by washing. These results suggested that tTG was involved in the early event of mouse oocyte maturation

• BMB Reports
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• 제39권5호
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• pp.586-594
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• 2006

Germinal centers (GCs) have been identified as site at which the somatic mutation of immunoglobulins occurs. However, somatic mutations in immunoglobulins have also been observed in animals that normally do not harbor germinal centers. This clearly indicates that somatic mutations can occur in the absence of germinal centers. We therefore attempted to determine whether or not GCs exist in TNFR1-deficient mice, and are essential for the somatic mutation of immunoglobulins, using (4-hydroxy-3-nitropheny)acetyl-ovalbumin (NP-OVA). Both wild-type and TNFR1-deficient mice were immunized with NPOVA, and then examined with regard to the existence of GCs. No typical B-cell follicles were detected in the TNFR1-deficient mice. Cell proliferation was detected throughout all splenic tissue types, and no in vivo immune-complex retention was observed in the TNFR1-deficient mice. All of these data strongly suggest that no GCs were formed in the TNFR1-deficient mice. Although TNFR1-deficient mice are unable to form GCs, serological analyses indicated that affinity maturation had been achieved in both the wild-type and TNFR1-deficient mice. We therefore isolated and sequenced several DNA clones from wild-type and the TNFR1-deficient mice. Eight out of 12 wild-type clones, and 11 out of 14 clones of the TNFR-1-deficient mice contained mutations at the CDR1 site. Thus, the wild-type and TNFR1-deficient mice were not extremely different with regard to types and rates of somatic mutation. Also, high-affinity antibodies were detected in both types of mice. Collectively, our data appear to show that affinity maturation may occur in TNFR1-deficient mice, which completely lack GCs.