• IMMUNE NETWORK
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• 제24권1호
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• pp.8.1-8.17
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• 2024

Follicular helper T cells (Tfh) play a crucial role in generating high-affinity antibodies (Abs) and establishing immunological memory. Cytokines, among other functional molecules produced by Tfh, are central to germinal center (GC) reactions. This review focuses on the role of cytokines, including IL-21 and IL-4, in regulating B cell responses within the GC, such as differentiation, affinity maturation, and plasma cell development. Additionally, this review explores the impact of other cytokines like CXCL13, IL-10, IL-9, and IL-2 on GC responses and their potential involvement in autoimmune diseases, allergies, and cancer. This review highlights contributions of Tfh-derived cytokines to both protective immunity and immunopathology across a spectrum of diseases. A deeper understanding of Tfh cytokine biology holds promise for insights into biomedical conditions.

• IMMUNE NETWORK
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• 제3권3호
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• pp.176-181
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• 2003

Background: The molecular basis of follicular dendritic cells (FDC)-germinal center (GC) B cell interaction is largely unknown, although this cellular interaction is thought to be important for the whole process of GC B cell differentiation. Methods: Using FDC-like cells, HK, and highly purified GC B cells, we attempted to identify the molecules that play critical roles in the interactions between FDC and B cells. GC B cells were co-cultured with HK cells and soluble CD154 in the presence or absence of various function-blocking monoclonal antibodies to examine their effect on GC B cell binding to HK cells and B cell proliferation. Results: Anti-CD11a and anti-CD54 antibodies inhibited GC B cell binding to HK cells while anti-CD49d and anti-CD106 antibodies did not. GC B cell proliferation was not impaired by the disruption of GC B cell-HK cell adherence. Conclusion: Our results suggest that CD11a/CD18-CD54 interactions play an important roles in the initial binding of GC B cells to FDC and diffusible growth factors from FDC may be responsible the massive proliferation of GC B cells.

• IMMUNE NETWORK
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• 제14권5호
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• pp.227-236
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• 2014

Understanding germinal center reactions is crucial not only for the design of effective vaccines against infectious agents and malignant cells but also for the development of therapeutic intervention for the treatment of antibody-mediated immune disorders. Recent advances in this field have revealed specialized subsets of T cells necessary for the control of B cell responses in the follicle. These cells include follicular regulatory T cells and Qa-1-restricted cluster of differentiation $(CD)8^+$ regulatory T cells. In this review, we discuss the current knowledge related to the role of regulatory T cells in the B cell follicle.

• 한국수정란이식학회지
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• 제10권3호
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• pp.183-191
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• 1995

This experiment was carried out to study the determination of survival of vitrified and thawed mammal follicular oocytes by FDA-test. Oocytes were divided into 3 groups according to attachment of cumulus cell. Group A oocytes were tightly surrounded by cumulus cell, group B oocytes were partially surrounded by cumulus cell, and group C oocytes were poorly surrounded by cumulus cell. Vitrification solution developed by our previous study (Kim et al, 1992) which consisted of permeable agent (20 % glycerol + 10 % ethylene glycol) and nonpermeable agent (30 % Ficoll + 10 % sucrose). Oocytes (7~10) loaded into 0.25 ml straw after 10 min equilibration were plunged into liquid nitrogen (- 196$^{\circ}C$) directly. The FDA-score of vitrified and thawed group A oocytes was higher in rat (4.2) than in rabbit (3.9), cow (3.8), mouse (3.4) and porcine (2.4), however that of cumulus cell was higher in rabbit (4.7) than in rat (4.1), cow (2.9), porcine (2.6) and mouse (1.4). The FDA-score of vitrified and thawed group B oocytes were 3.1 (cow), 2.9 (rabbit), 2.9 (mouse), 2.6 (rat) and 2.5 (porcine), respectively. However that of cumulus cell was higher in rabbit (3.7) than in porcine (2.6), rat (2.3), cow (1.7) and mouse (0.3). The FDA-score of vitrified and thawed group C oocytes was higher in mouse (4.1) than in cow (2.9), rabbit (2.6), rat (1.3) and porcine (1.1). As shown in the above results, The survival rates of oocytes were higher in group A than in group B and C except in mouse and cow. These results suggest that the survival of cumulus cell as well as follicular oocytes can be reliably judged by their fluorescence with FDA-test.

• IMMUNE NETWORK
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• 제1권1호
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• pp.26-31
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• 2001

Background : Follicular dendritic cells (FDCs) play key roles during T cell-dependent humoral immune responses by allowing antigen-specific B cells to survive, proliferate, and differentiate within the FDC networks of secondary follicles, i.e., germinal centers (GC). Methods: A novel monoclonal antibody, 3C8, was generated by immunizing with an FDC line HK, in order to understand the molecular signals involved in the FDC-B cell interactions in the microenvironment of the GC. Results: The 3C8 antibody did not bind to mononuclear cells, including T cells, B cells, and monocytes. Murine L929 and human skin fibroblasts exhibited no or little reactivity to 3C8. However, 3C8 specifically recognized HK cells by flowcytometry. Furthermore, the antigen recognized by 3C8 was restricted to the GC of the human tonsil. Dendritic networks of the GC were intensely stained by 3C8, but cells outside the GC were not. Conclusion: Our results suggest that the antigen 3C8 may play some unique role on FDCs during the GC reactions.

• 대한두경부종양학회지
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• 제34권1호
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• pp.49-53
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• 2018

Primary non-Hodgkin's lymphoma (NHL) rarely involves the parotid gland and its incidence is only 1.7% to 3.1% of all salivary gland neoplasms. The mucosa associated lymphoid tissue (MALT) is the most common subtype of NHL, followed by follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL). However, two distinct types of lymphomas occurring synchronously in the parotid gland and cervical lymph node have not been reported earlier. A 72-year-old man with rubbery-hard and fixed mass on the left parotid area came to our clinic. We performed the left total parotidectomy with ipsilateral excision of lymph node (level II), and he was finally diagnosed as DLBCL in parotid gland and FL in upper neck. It is presumed that the DLBCL appeared to be a transformation from FL. We report the unique and rare disease entity with brief literature review.

• 한국가축번식학회지
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• 제14권2호
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• pp.93-100
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• 1990

These experiments were carried out to investigate the effect of rabbit anti-bovine cumulus cell antibodies on in vitro maturation of bovine follicular oocytes. Antisera to bovine cumulus cell were produced Japanese Ginat rabbit by repeated immunization of intact or solubilized bovine cumulus cell and purified by ammonium sulfate precipitation and Sepharose CL-4B protein-A affinity chromatography. The bovine cumulus cell-specific antibodies were confirmed by indirect ELISA. The results obtained in these experiments were summarized as follows : 1. The titer of the antibodies to cumulus cell determined by indirect ELISA using intact or solubilized bovine cumulus cell coated plates was very high in both intact and solubilized cumulus cells. Namely, the optical density at 1:12,800 dilution of antibodies was still significantly higher than that of non-immunized control serum. 2. When the follicular oocytes were treated with antibody to intact cumulus cells, the maturation rate of cumulus compacted and removed oocytes was ranged 47.6 to 59.1%. These value is significantly lower(p<0.05) than that(78.8%) of follicular oocytes cultured without the antibody. 3. the maturation rate of cumulus compacted and removed oocytes treated with antibody to solubilized cumulus cells was ranged 46.7 to 59.1%, significantly lower(p<0.05) than that(82.1%) of ooyctes cultured in antibody free medium. From above mentioned results, it could be said that cumulus cells promote nuclear maturation of follicular oocytes and that the beneficial effect of cumulus cells to the oocyte maturation is inhibited by the action of antibody to cumulus cells.

• Molecules and Cells
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• 제38권3호
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• pp.195-201
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• 2015

Antibodies are powerful defense tools against pathogens but may cause autoimmune diseases when erroneously directed toward self-antigens. Thus, antibody producing cells are carefully selected, refined, and expanded in a highly regulated microenvironment (germinal center) in the peripheral lymphoid organs. A subset of T cells termed T follicular helper cells (Tfh) play a central role in instructing B cells to form a repertoire of antibody producing cells that provide life-long supply of high affinity, pathogenspecific antibodies. Therefore, understanding how Tfh cells arise and how they facilitate B cell selection and differentiation during germinal center reaction is critical to improve vaccines and better treat autoimmune diseases. In this review, I will summarise recent findings on molecular and cellular mechanisms underlying Tfh generation and function with an emphasis on T cell costimulation.

• IMMUNE NETWORK
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• 제14권1호
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• pp.21-29
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• 2014

Follicular helper T ($T_{FH}$) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, na$\ddot{i}$ve T cells are differentiating into $T_{FH}$ cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). $T_{FH}$ cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and $T_{FH}$ cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in $T_{FH}$ cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and $T_{FH}$ cell differentiation. $T_{FH}$ cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of $T_{FH}$ cells. The miR-17-92 cluster induces Bcl-6 and $T_{FH}$ cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T ($T_{FR}$) cells are studied as thymus-derived $CXCR5^+PD-1^+Foxp3^+\;T_{reg}$ cells that play a significant role in limiting the GC response. Regulation of $T_{FH}$ cell differentiation and the GC reaction via miRNA and $T_{FR}$ cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect $T_{FH}$ cell differentiation, and the role of $T_{FH}$ cells in autoimmune diseases.

• 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.