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RnDSy-lu-2945 Follicular Helper T Cells Plasma B Cell Tfh Cell Memory B Cell Centrocyte Follicular Helper T Cells & Regulation of B Cell Immunity Follicular helper T (Tfh) cells represent a functional subset of CD4+ of the B cell follicle where they interact with antigen-primed B cells (). helper T (Th) cells that provides help for B cells to allow the formation of The T cells also respond to IL-6 with the activation of the transcription plasma cells and long-lived memory B cells. Tfh cells are characterized factors cMAF and STAT3, and the induction of IL-21 expression. IL-6 and by the elevated expression of CXCR5, CD40L, OX40, ICOS, PD-1, Bcl-6, the autocrine action of IL-21 stimulate activated T cells to express Bcl-6, SLAM receptors, and IL-21. Though other Th subsets express these the master transcription factor that controls Tfh cell differentiation. Bcl- proteins, it is the relatively high expression levels that delineates Tfh 6, a transcriptional repressor, suppresses factors that mediate the cells and enhances their capacity to facilitate antibody production. Tfh differentiation of Th1, Th2, and Th17 cells. In addition, Bcl-6 indirectly cells are believed to be involved in angioimmunoblastic T cell lymphoma induces the expression of accessory proteins, such as CXCR4 and PD-1, and several autoimmune diseases, including systemic lupus by repressing clusters of microRNAs that negatively regulate these erythematosus and Sjogren’s syndrome. molecules. The synergistic actions of Bcl-6 and cMAF, in conjunction with CD28, OX40, and ICOS stimulation in Tfh cells, induce a sustained Though the complete differentiation process for Tfh cells is still being increase in CXCR5 expression. CXCR5 directs migration into B cell investigated, it has been shown that naïve CD4+ T (Th0) cells expressing follicles where Tfh cells interact with germinal center B cells called CCR7 chemokine receptor are chemoattracted to the T cell zone of the centrocytes (). Tfh cells secrete IL-10, IL-21, and small amounts of IL-2, secondary lymphoid tissue by CCL19 and CCL21 (). In the T cell zone, IL-4, IL-17, and IFN-g, to stimulate centrocytes to generate antibody- Th0 cells are activated by antigen-presenting dendritic cells and express producing plasma cells and memory B cells (). CD40L, OX40, and ICOS (). These activated T cells migrate to the edge B Cell Follicle T Cell Zone L-Selectin ThO CCeellll CCL19CL19,, CCCCRCCR7R7R CCCCL21L21 CD4D4+CD3- TTCCR-R-CDCD33 Accessory CCeellll CCDD44 CD28CD28 CXCXCL13CL13 TThhOO CCeellll Lymph Node CCCCR7R7 CCCCR7R7 IL--66 FFoolollicularllicccuuulalara IL-6 Rα SStStromalror mmalCl Celleellss TTCCR-R-CDCD33 CD28CD28 gp130gp130 MHCMMH II IL-21 B7 IL-21-21 R IILL--22 Rγ gp130 CXXCCL13L1L133 CD4C CCCCL21L21 IL-2, IL-4, TfhTfh CCeellll CCCCL19L19 IL-10,10 IL-17,17 SAS P DendriticDendriticC Cellell IL-21, IFN-γ SSLAMLAM CXXCCCR4R4 PDPD-1-1 CD69 CD40CCD L ICOOSS CXCXCXCRCR5R55 SSLAMLAM TCR-CD3 CXXXCCL13CL1L13L133 ILIL-21 PDPD-L1-L1 CeCentrntrooccyytete CDCD44 CXCXCR5CR5 ILIL-21 R ICOS L STAT3 MHCMHC IIII MemorMemory B CCeellslls IILL-2 Rγ CXCRCR55 CXCXXCCL13CLL131313 OX40 CD40CCD L AcActtivatedivated T CCeellll CXCRCR5R55 CD28 BCRBCR OX40 L ICOS gp130gp1gp 30 CXCR5 gp130gp130 Antigen IL--66 CXCXCL13CL13 B7 CR/FccRR CeC ntroblastsntrooboblablb asttsts B CCeellll IL-6 Rα PPlasmalasma CeCellslls ICOSOS L CCCCL19,L19, CCCCL21L21 FoFollicularllicular DendriticDendritic Cell CCCCR7R7 Germinal Center Light Zone Germinal Center Dark Zone Cortex This illustration represents general pathways suggested in the scientific literature and is not to be considered comprehensive nor definitive. Abbreviation Key Bcl-6 B cell lymphoma-6 PD-1 Programmed Death-1 CD40 L CD40 Ligand PD-L1 Programmed Death Ligand-1 CR Complement Receptor SAP SLAM-associated Protein FcR Fc Receptor SLAM Signaling Lymphocytic Activation Molecule Receptor Family ICOS Inducible T cell Co-stimulator STAT3 Signal Transducer and Activator of Transcription 3 ICOS L ICOS Ligand OX40 L OX40 Ligand Follicular Helper T Cell-Related Products Recombinant & Recombinant & Molecule Antibodies ELISAs Molecule Antibodies ELISAs Natural Proteins Natural Proteins 2B4/CD244/SLAMF4 H M H M H M R P B Ca CR E F H M R P B Ca CR H M R P Ca IL-4 Rb RM E F Rb CR E F Rb Akt H M R H M R IL-4 Ra H M H M B7-H2/ICOS Ligand H M H M IL-5 H M R P B Ca E F RM H M R P Ca E F H M F Bcl-6 H M H M R P Ca CR E H M R P B Ca BLAME/SLAMF8 H H M IL-6 H M R P Ca CR E F F Pr CR F Rb BLIMP1 H M IL-6 Ra H M H M H M BTLA/CD272 H M H M H M R P Ca CR E H M R P Ca E IL-10 H M R P Ca CR E F V CCL19/MIP-3b H M R H M R H M F V F GP CCL21/6Ckine H M R H M H M IL-13 H M R Ca CR RM H M R Ca H M CCR7 H M IL-17/IL-17A H M R Ca H M Ca Pr H M Ca CD2F-10/SLAM9 H M M IL-21 H M Ca Rb M Ca M CD4 H R CR F H M R Ca CR F IL-21 R H M R H M CD10/Neprilysin H M H M H M Jak1 H M R CD21 H H Jak2 M R CD28 H M H M NFATC1 H CD30/TNFRSF8 H M H M H M NTB-A/SLAMF6/ H M H M Ly-108 CD30 Ligand/TNFSF8 H M H M M OX40/TNFRSF4 H M R H M CD35 H H OX40 Ligand/TNFSF4 H M R H M M CD40/TNFRSF5 H M R H M H M PD-1 H M CM H M H M CD40 Ligand/TNFSF5 H M R H M H M PD-L1/B7-H1 H M H M H CM CD48/SLAMF2 H M H M M PD-L2 H M CM H M H CD69 H M H M PI 3-Kinase p55g H M R CD84/SLAMF5 H M H PI 3-Kinase p85a H M R CD200 H M H M R H PI 3-Kinase p85b H CD200 R1 H M H M PI 3-Kinase p110b H CD229/SLAMF3 H M H M PI 3-Kinase p110d H CRACC/SLAMF7 M H M PI 3-Kinase p110g H CXCL13/BLC/BCA-1 H M H M H M PTEN H H M R CXCR4 H M F SHP-1 H H M R CXCR5 H M SHP-2 H H M R H M R Fas/TNFRSF6/CD95 H M R F H M R F H M SLAM/CD150 H M H M H M Fcg RII/CD32 H M STAT3 H M R H M GATA-3 H M Tyk2 H ICOS H M H M Vav-1 H M H M R P B Ca CR E F H M R P B Ca CR H M R P B Ca IFN-g RM V E F RM CR E F Pr H Human M Mouse R Rat B Bovine Ca Canine CM Cynomolgus Monkey CR Cotton Rat E Equine F Feline GP Guinea Pig P Porcine Pr Primate Rb Rabbit RM Rhesus Macaque V Viral IL-21 R (µg/mL) 0.001 0.01 0.1 1 10 100 2000 2000 1800 1800 Cell Proliferation (Mean RFU) Proliferation Cell 1600 1600 1400 1400 1200 1200 1000 1000 Cell Proliferation (Mean RFU) Proliferation Cell 800 800 600 600 0.01 0.1 1 10 100 1000 IL-21 (ng/mL) Inhibition of IL-21 Activity by Soluble IL-21 Receptor. Recombinant Mouse IL-21 (Catalog ICOS in Human Tonsil. ICOS was detected in paraffin-embedded human tonsil tissue sec- # 594-ML) stimulates the proliferation of N1186 HTLV-1-infected human T cells (red line), tions using the Human ICOS Antigen Affinity-purified Polyclonal Antibody (Catalog # AF169). measured by resazurin fluorescence (Catalog # AR002). The stimulatory effect induced by The tissue was stained using the Anti-Goat HRP-DAB Cell and Tissue Staining Kit (Catalog 100 ng/mL IL-21 was inhibited in a dose-dependent manner by soluble Recombinant # CTS008; brown) and counterstained with hematoxylin (blue). Mouse IL-21 R (Catalog # 596-MR; blue line). Tocri-24 RnDSy-24 Novus-24 Global [email protected] bio-techne.com/find-us/distributors TEL +1 612 379 2956 North America TEL 800 343 7475 Europe | Middle East | Africa TEL +44 (0)1235 529449 China [email protected] TEL +86 (21) 52380373 bio-techne.com For research use or manufacturing purposes only. Trademarks and registered trademarks are the property of their respective owners. BR_Follicular Helper T Cells_6025.
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