T Cell Help to B Cells in Germinal Centers: Putting the Jigsaw Together

REFERENCES

• Rajewsky K, Schirrmacher V, Nase S, Jerne NK. The requirement of more than one antigenic determinant for immunogenicity. J Exp Med 1969; 129: 1131– 1143.
   PubMed Web of Science ®Google Scholar
• Miller JF. Immunological function of the thymus. Lancet 1961; 2: 748–749.
   PubMed Web of Science ®Google Scholar
• Claman HN, Chaperon EA, Triplett RF. Thymus-marrow cell combinations. Synergism in antibody production. Proc Soc Exp Biol Med 1966; 122: 1167–1171.
   PubMed Web of Science ®Google Scholar
• Parker DC. T cell-dependent B cell activation. Annu Rev Immunol 1993; 11: 331–360.
   PubMed Web of Science ®Google Scholar
• Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature 1985; 314: 537–539.
   PubMed Web of Science ®Google Scholar
• McHeyzer-Williams LJ, McHeyzer-Williams MG. Antigen-specific memory B cell development. Annu Rev Immunol 2005; 23: 487–513.
   PubMed Web of Science ®Google Scholar
• Vinuesa CG, Tangye SG, Moser B, Mackay CR. Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol 2005; 5: 853–865.
   PubMed Web of Science ®Google Scholar
• Ettinger R, Kuchen S, Lipsky PE. The role of IL-21 in regulating B-cell function in health and disease. Immunol Rev 2008; 223: 60–86.
   PubMed Web of Science ®Google Scholar
• Suvas S, Singh V, Sahdev S, Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma. J Biol Chem 2002; 277: 7766–7775.
   PubMed Web of Science ®Google Scholar
• Quezada SA, Jarvinen LZ, Lind EF, Noelle RJ. CD40/CD154 interactions at the interface of tolerance and immunity. Annu Rev Immunol 2004; 22: 307–328.
   PubMed Web of Science ®Google Scholar
• Allen CD, Okada T, Cyster JG. Germinal-center organization and cellular dynamics. Immunity 2007; 27: 190–202.
   PubMed Web of Science ®Google Scholar
• MacLennan IC. Germinal centers. Annu Rev Immunol 1994; 12: 117–139.
   PubMed Web of Science ®Google Scholar
• Klein U, Dalla-Favera R. Germinal centres: Role in B-cell physiology and malignancy. Nat Rev Immunol 2008; 8: 22–33.
   PubMed Web of Science ®Google Scholar
• Mosmann TR, Cherwinski H, Bond MW, Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136: 2348–2357.
   PubMed Web of Science ®Google Scholar
• Mosmann TR, Coffman RL. TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989; 7: 145–173.
   PubMed Web of Science ®Google Scholar
• Snapper CM, Paul WE. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science 1987; 236: 944–947.
   PubMed Web of Science ®Google Scholar
• Stevens TL, Bossie A, Sanders VM, Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature 1988; 334: 255–258.
   PubMed Web of Science ®Google Scholar
• Boom WH, Liano D, Abbas AK. Heterogeneity of helper/inducer T lymphocytes. II. Effects of interleukin 4- and interleukin 2-producing T cell clones on resting B lymphocytes. J Exp Med 1988; 167: 1350–1363.
   PubMed Web of Science ®Google Scholar
• Finkelman FD, Holmes J, Katona IM, Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol 1990; 8: 303–333.
   PubMed Web of Science ®Google Scholar
• Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol 2010; 28: 445–489.
   PubMed Web of Science ®Google Scholar
• Zhou L, Chong MM, Littman DR. Plasticity of CD4+ T cell lineage differentiation. Immunity 2009; 30: 646–655.
   PubMed Web of Science ®Google Scholar
• Locksley RM. Nine lives: Plasticity among T helper cell subsets. J Exp Med 2009; 206: 1643–1646.
   PubMed Web of Science ®Google Scholar
• Reinhardt RL, Liang HE, Locksley RM. Cytokine-secreting follicular T cells shape the antibody repertoire. Nat Immunol 2009; 10: 385–393.
   PubMed Web of Science ®Google Scholar
• Schaerli P, Willimann K, Lang AB, CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 2000; 192: 1553–1562.
   PubMed Web of Science ®Google Scholar
• Breitfeld D, Ohl L, Kremmer E, Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med 2000; 192: 1545–1552.
   PubMed Web of Science ®Google Scholar
• Chtanova T, Tangye SG, Newton R, T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J Immunol 2004; 173: 68–78.
   PubMed Web of Science ®Google Scholar
• Vinuesa CG, Tangye SG, Moser B, Mackay CR. Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol 2005; 5: 853–865.
   PubMed Web of Science ®Google Scholar
• King C, Tangye SG, Mackay CR. T follicular helper (TFH) cells in normal and dysregulated immune responses. Annu Rev Immunol 2008; 26: 741–766.
   PubMed Web of Science ®Google Scholar
• Fazilleau N, Mark L, McHeyzer-Williams LJ, McHeyzer-Williams MG. Follicular helper T cells: Lineage and location. Immunity 2009; 30: 324–335.
   PubMed Web of Science ®Google Scholar
• Catron DM, Itano AA, Pape KA, Visualizing the first 50 hr of the primary immune response to a soluble antigen. Immunity 2004; 21: 341–347.
   PubMedGoogle Scholar
• Bromley SK, Mempel TR, Luster AD. Orchestrating the orchestrators: Chemokines in control of T cell traffic. Nat Immunol 2008; 9: 970–980.
   PubMed Web of Science ®Google Scholar
• Reif K, Ekland EH, Ohl L, Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position. Nature 2002; 416: 94–99.
   PubMed Web of Science ®Google Scholar
• Haynes NM, Allen CD, Lesley R, Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1 high germinal center-associated subpopulation. J Immunol 2007; 179: 5099–5108.
   PubMed Web of Science ®Google Scholar
• Hardtke S, Ohl L, Forster R. Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help. Blood 2005; 106: 1924–1931.
   PubMed Web of Science ®Google Scholar
• MacLennan IC, Toellner KM, Cunningham AF, Extrafollicular antibody responses. Immunol Rev 2003; 194: 8–18.
   PubMed Web of Science ®Google Scholar
• Allen CD, Cyster JG. Follicular dendritic cell networks of primary follicles and germinal centers: Phenotype and function. Semin Immunol 2008; 20: 14–25.
   PubMed Web of Science ®Google Scholar
• Suzuki K, Grigorova I, Phan TG, Visualizing B cell capture of cognate antigen from follicular dendritic cells. J Exp Med 2009; 206: 1485–1493.
   PubMed Web of Science ®Google Scholar
• Allen CD, Okada T, Tang HL, Cyster JG. Imaging of germinal center selection events during affinity maturation. Science 2007; 315: 528–531.
   PubMed Web of Science ®Google Scholar
• Allen CD, Ansel KM, Low C, Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5. Nat Immunol 2004; 5: 943–952.
   PubMed Web of Science ®Google Scholar
• Muramatsu M, Kinoshita K, Fagarasan S, Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 2000; 102: 553–563.
   PubMed Web of Science ®Google Scholar
• Harriman W, Volk H, Defranoux N, Wabl M. Immunoglobulin class switch recombination. Annu Rev Immunol 1993; 11: 361–384.
   PubMed Web of Science ®Google Scholar
• Ozaki K, Spolski R, Feng CG, A critical role for IL-21 in regulating immunoglobulin production. Science 2002; 298: 1630–1634.
   PubMed Web of Science ®Google Scholar
• Nurieva RI, Chung Y, Hwang D, Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 2008; 29: 138–149.
   PubMed Web of Science ®Google Scholar
• Coffey F, Alabyev B, Manser T. Initial clonal expansion of germinal center B cells takes place at the perimeter of follicles. Immunity 2009; 30: 599–609.
   PubMed Web of Science ®Google Scholar
• McHeyzer-Williams MG, McLean MJ, Lalor PA, Nossal GJ. Antigen-driven B cell differentiation in vivo. J Exp Med 1993; 178: 295–307.
   PubMed Web of Science ®Google Scholar
• Zaheen A, Boulianne B, Parsa JY, AID constrains germinal center size by rendering B cells susceptible to apoptosis. Blood 2009; 114: 547–554.
   PubMed Web of Science ®Google Scholar
• Vogelzang A, McGuire HM, Yu D, A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity 2008; 29: 127–137.
   PubMed Web of Science ®Google Scholar
• Nurieva RI, Chung Y, Martinez GJ, Bcl6 mediates the development of T follicular helper cells. Science 2009; 325: 1001–1005.
   PubMed Web of Science ®Google Scholar
• Johnston RJ, Poholek AC, DiToro D, Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 2009; 325: 1006–1010.
   PubMed Web of Science ®Google Scholar
• Yu D, Rao S, Tsai LM, The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 2009; 31: 457–468.
   PubMed Web of Science ®Google Scholar
• King IL, Mohrs M. IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells. J Exp Med 2009; 206: 1001– 1007.
   PubMedGoogle Scholar
• Zaretsky AG, Taylor JJ, King IL, T follicular helper cells differentiate from Th2 cells in response to helminth antigens. J Exp Med 2009; 206: 991–999.
   PubMedGoogle Scholar
• Tsuji M, Komatsu N, Kawamoto S, Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 2009; 323: 1488–1492.
   PubMed Web of Science ®Google Scholar
• Fazilleau N, McHeyzer-Williams LJ, Rosen H, McHeyzer-Williams MG. The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding. Nat Immunol 2009; 10: 375–384.
   PubMed Web of Science ®Google Scholar
• Hsu HC, Yang P, Wang J, Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol 2008; 9: 166–175.
   PubMed Web of Science ®Google Scholar
• Crotty S, Johnston RJ, Schoenberger SP. Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation. Nat Immunol 2010; 11: 114–120.
   PubMed Web of Science ®Google Scholar
• Schaerli P, Loetscher P, Moser B. Cutting edge: Induction of follicular homing precedes effector Th cell development. J Immunol 2001; 167: 6082–6086.
   PubMed Web of Science ®Google Scholar
• Linterman MA, Rigby RJ, Wong RK, Follicular helper T cells are required for systemic autoimmunity. J Exp Med 2009; 206: 561–576.
   PubMed Web of Science ®Google Scholar
• Mak TW, Shahinian A, Yoshinaga SK, Costimulation through the inducible costimulator ligand is essential for both T helper and B cell functions in T cell-dependent B cell responses. Nat Immunol 2003; 4: 765–772.
   PubMed Web of Science ®Google Scholar
• Tafuri A, Shahinian A, Bladt F, ICOS is essential for effective T-helper-cell responses. Nature 2001; 409: 105–109.
   PubMed Web of Science ®Google Scholar
• McAdam AJ, Greenwald RJ, Levin MA, ICOS is critical for CD40-mediated antibody class switching. Nature 2001; 409: 102–105.
   PubMed Web of Science ®Google Scholar
• Crotty S, Kersh EN, Cannons J, SAP is required for generating long-term humoral immunity. Nature 2003; 421: 282–287.
   PubMed Web of Science ®Google Scholar
• Qi H, Cannons JL, Klauschen F, SAP-controlled T-B cell interactions underlie germinal centre formation. Nature 2008; 455: 764–769.
   PubMed Web of Science ®Google Scholar
• Cannons JL, Qi H, Lu KT, Optimal germinal center responses require a multistage T cell: B cell adhesion process involving integrins, SLAM-associated protein, and CD84. Immunity 2010; 32: 253–265.
   PubMed Web of Science ®Google Scholar
• Baccam M, Woo SY, Vinson C, Bishop GA. CD40-mediated transcriptional regulation of the IL-6 gene in B lymphocytes: Involvement of NF-kappa B, AP-1, and C/EBP. J Immunol 2003; 170: 3099–3108.
   PubMed Web of Science ®Google Scholar
• Urashima M, Chauhan D, Hatziyanni M, CD40 ligand triggers interleukin-6 mediated B cell differentiation. Leuk Res 1996; 20: 507–515.
   PubMed Web of Science ®Google Scholar
• Odegard JM, Marks BR, DiPlacido LD, ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity. J Exp Med 2008; 205: 2873–2886.
   PubMed Web of Science ®Google Scholar
• Han S, Hathcock K, Zheng B, Cellular interaction in germinal centers. Roles of CD40 ligand and B7–2 in established germinal centers. J Immunol 1995; 155: 556–567.
   PubMed Web of Science ®Google Scholar
• Good-Jacobson KL, Szumilas CG, Chen L, PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol 2010; 11: 535–542.
   PubMed Web of Science ®Google Scholar
• Spolski R, Leonard WJ. Interleukin-21: Basic biology and implications for cancer and autoimmunity. Annu Rev Immunol 2008; 26: 57–79.
   PubMed Web of Science ®Google Scholar
• Jin H, Carrio R, Yu A, Malek TR. Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis. J Immunol 2004; 173: 657–665.
   PubMed Web of Science ®Google Scholar
• Zotos D, Coquet JM, Zhang Y, IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. J Exp Med 2010; 207: 365–378.
   PubMed Web of Science ®Google Scholar
• Linterman MA, Beaton L, Yu D, IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J Exp Med 2010; 207: 353–363.
   PubMed Web of Science ®Google Scholar
• Meyer-Hermann M, Figge MT, Toellner KM. Germinal centres seen through the mathematical eye: B-cell models on the catwalk. Trends Immunol 2009; 30: 157–164.
   PubMedGoogle Scholar
• Phan TG, Paus D, Chan TD, High affinity germinal center B cells are actively selected into the plasma cell compartment. J Exp Med 2006; 203: 2419–2424.
   PubMed Web of Science ®Google Scholar
• Wei G, Wei L, Zhu J, Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity 2009; 30: 155–167.
   PubMed Web of Science ®Google Scholar