Signaling and Gene Expression in the Immune System

Symposium Participants    v Foreword    xxi

Lymphocyte Development

Lymphoid Development from Stem Cells and the Common Lymphocyte Progenitors K. Akashi, M. Kondo, S. Cheshier, J. Shizuru, K. Gandy, J. Domen, R. Mebius, D. Traver, and I.L. Weissman    1 PU.1, a Shared Transcriptional Regulator of Lymphoid and Myeloid Cell Fates H. Singh, R.P. DeKoter, and J.C. Walsh    13 Differentiation, Dedifferentiation, and Redifferentiation of B-lineage Lymphocytes: Roles of the Surrogate Light Chain and the Pax5 Gene A. Rolink, S. Nutt, M. Busslinger, E. ten Boekel, T. Seidl, J. Andersson, and F. Melchers    21 Notch and the CD4 Versus CD8 Lineage Decision P. Valdez and E. Robey    27 Consequences of Notch-mediated Inhibition of the Transcription Factor E47 W. Pear, Z. Tang, S. DeRocco, D. Allman, R. Hardy, J. Pui, L. Xu, F. Karnell, J. Aster, and T. Kadesch    33 Role of Helix-Loop-Helix Proteins in Lymphocyte Development C. Murre    39 Controlling Lymphopoiesis with a Combinatorial E-protein Code R.J. Barndt and Y. Zhuang    45 The Molecular Basis of B-cell Lineage Commitment S.L. Nutt, A.G. Rolink, and M. Busslinger    51 Role of B-lymphocyte-induced Maturation Protein-1 in Terminal Differentiation of B Cells and Other Cell Lineages C. Angelin-Duclos, G. Cattoretti, D.H. Chang, K.-I. Lin, Y. Lin, J. Yu, and K. Calame    61 The Lymphochip: A Specialized cDNA Microarray for the Genomic-scale Analysis of Gene Expression in Normal and Malignant Lymphocytes A. Alizadeh, M. Eisen, R.E. Davis, C. Ma, H. Sabet, T. Tran, J.I. Powell, L. Yang, G.E. Marti, D.T. Moore, J.R. Hudson, Jr., W.C. Chan, T. Greiner, D. Weisenburger, J.O. Armitage, I. Lossos, R. Levy, D. Botstein, P.O. Brown, and L.M. Staudt    71

Transcription Factors and the Control of Lymphocyte Development

Ikaros Chromatin Remodeling Complexes in the Control of the Differentiation of the Hemo-lymphoid System J. Koipally, J. Kim, B. Jones, A. Jackson, N. Avitahl, S. Winandy, M. Trevisan, A. Nichogiannopoulou, C. Kelley, and K. Georgopoulos    79 Mechanisms of Transcriptional Regulation in Lymphocyte Progenitors: Insight from an Analysis of the Terminal Transferase Promoter P. Ernst, K. Hahm, B.S. Cobb, K.E. Brown, L.A. Trinh, A.S. McCarty, M. Merkenschlager, C.A. Klug, A.G. Fisher, and S.T. Smale    87 Mechanisms of m Enhancer Regulation in B Lymphocytes B.S. Nikolajczyk, W. Dang, and R. Sen    99 Differential Regulation of Immunoglobulin Gene Transcription via Nuclear Matrix-associated Regions C. Webb, R.-T. Zong, D. Lin, Z. Wang, M. Kaplan, Y. Paulin, E. Smith, L. Probst, J. Bryant, A. Goldstein, R. Scheuermann, and P. Tucker    109 B-cell-specific Coactivator OCA-B: Biochemical Aspects, Role in B-Cell Development and Beyond Y. Luo and R.G. Roeder    119 Control of Lymphocyte Differentiation by the LEF-1/TCF Family of Transcription Factors T. Reya, R. Okamura, and R. Grosschedl    133 Activation and Repression of Wingless/Wnt Target Genes by the TCF/LEF-1 Family of Transcription Factors H.C. Korswagen and H.C. Clevers    141 The INF-b Enhancer: A Paradigm for Understanding Activation and Repression of Inducible Gene Expression N. Munshi, J. Yie, M. Merika, K. Senger, S. Lomvardas, T. Agalioti, and D. Thanos    149

Recombination and Allelic Exclusion

V(D)J Recombination: Links to Transposition and Double-strand Break Repair M. Gellert, J.E. Hesse, K. Hiom, M. Melek, M. Modesti, T.T. Paull, D.A. Ramsden, and D.C. van Gent    161 Nonhomologous End-joining Proteins Are Required for V(D)J Recombination, Normal Growth, and Neurogenesis J.M. Sekiguchi, Y. Gao, Y. Gu, K. Frank, Y. Sun, J. Chaudhuri, C. Zhu, H.-L. Cheng, J. Manis, D. Ferguson, L. Davidson, M.E. Greenberg, and F.W. Alt    169 Regulation of Chromatin Accessibility for V(D)J Recombination C. Hernandez-Munain, M. Taylor McMurry, and M.S. Krangel    183 What Prevents Intermolecular V(D)J Recombination? L.E. Huye, J.-O. Han, and D.B. Roth    191 Demethylation and the Establishment of k Allelic Exclusion R. Mostoslavsky, A. Kirillov, Y.-H. Ji, M. Goldmit, M. Holzmann, T. Wirth, H. Cedar, and Y. Bergman    197 RAG Expression in B Cells in Secondary Lymphoid Tissues W. Yu, H. Nagaoka, Z. Misulovin, E. Meffre, H. Suh, M. Jankovic, N. Yannoutsos, R. Casellas, E. Besmer, F. Papavasiliou, X. Qin, and M.C. Nussenzweig    207 Antibody Diversification and Selection in the Mature B-Cell Compartment M.S. Neuberger, A. Lanoue, M.R. Ehrenstein, F.D. Batista, J.E. Sale, and G.T. Williams    211 Molecular Mechanism of Immunoglobulin Class Switch Recombination K. Kinoshita, C.-G. Lee, J. Tashiro, M. Muramatsu, X.-C. Chen, K. Yoshikawa, and T. Honjo    217 Molecular Aspects of Somatic Hypermutation of Immunoglobulin Genes U. Storb, A. Peters, N. Kim, H.M. Shen, G. Bozek, N. Michael, J. Hackett, Jr., E. Klotz, J.D. Reynolds, L.A. Loeb, and T.E. Martin    227

T-cell Activation and Receptor Signaling

Structural, Biochemical, and Biophysical Studies of HLA-A2/Altered Peptide Ligands Binding to Viral-peptide-specific Human T-cell Receptors B.M. Baker, Y.-H. Ding, D.N. Garboczi, W.E. Biddison, and D.C. Wiley    235 Visualizing T-cell Recognition M.M. Davis, C. Wülfing, M.F. Krummel, P.A. Savage, J. Xu, C. Sumen, M.L. Dustin, and Y.-H. Chien    243 Three Signals and a Master Switch in the Regulation of T-cell Immunity A. Lanzavecchia    253 Studies on the Adapter Molecule LAT L.E. Samelson, S.C. Bunnell, R.P. Trible, T. Yamazaki, and W. Zhang    259 The Adapter Proteins LAT and SLP-76 Are Required for T-cell Activation T.S. Finco, D. Yablonski, J. Lin, and A. Weiss    265 Signaling in Primary Thymocytes after Presentation of Altered Peptide Ligands by Antigen- presenting Cells or MHC-peptide Tetramers L.A. Smyth, L. Reynolds, R. Tyrrell, O. Williams, T. Norton, T. Schumacher, V. Tybulewicz, S.C. Ley, and D. Kioussis    275 The Impact of Pre-T-cell Receptor Signals on Gene Expression in Developing T Cells H. von Boehmer, I. Aifantis, O. Azogui, C. Saint-Ruf, and F. Grassi    283 The PTK-STAT Signaling Pathway Has Essential Roles in T-cell Activation in Response to Antigen Stimulation T. Welte, D. Leitenberg, B.N. Dittel, B.K. al-Ramadi, W.R. Hansen, B. Xie, C.A. Janeway, Jr., A.L.M. Bothwell, K. Bottomly, and X.-Y. Fu    291 CTLA-4 -The Costimulatory Molecule That Doesn't: Regulation of T-cell Responses by Inhibition C.A. Chambers and J.P. Allison    303

B-cell Activation and Receptor Signaling

Mechanisms of Self-tolerance and Autoimmunity: From Whole-animal Phenotypes to Molecular Pathways C.C. Goodnow, R. Glynne, D. Mack, B. Weintraub, J. Rathmell, J.I. Healy, S. Chaudhry, L. Miosge, A. Loy, and L. Wilson    313 The Maintenance and the Activation Signal of the B-cell Antigen Receptor M. Reth and J. Wienands    323 Inhibitory Receptors and Their Modes of Action D.C. Fong and J.C. Cambier    329

Cell Death and Survival in the Immune System

Genetic Analysis of Apoptotic and Survival Signals T.W. Mak and W.-C. Yeh    335 Death and Survival Signals Determine Active/Inactive Conformations of Pro-apoptotic BAX, BAD, and BID Molecules S.J. Korsmeyer, A. Gross, H. Harada, J. Zha, K. Wang, X.-M. Yin, M. Wei, and S. Zinkel    343 Control of Apoptosis in Hematopoietic Cells by the Bcl-2 Family of Proteins J.M. Adams, D.C.S. Huang, H. Puthalakath, P. Bouillet, G. Vairo, K. Moriishi, G. Hausmann, L. O'Reilly, K. Newton, S. Ogilvy, M.L. Bath, C.G. Print, A.W. Harris, A. Strasser, and S. Cory    351 RIPs: An Emerging Family of Kinases Involved in Pro-inflammatory and Apoptotic Signaling V.M. Dixit    359 Receptor-mediated Apoptosis in T Lymphocytes J. Zhang, A. DeYoung, H.G. Kasler, N.H. Kabra, A.A. Kuang, G. Diehl, S.J. Sohn, C. Bishop, and A. Winoto    363 Role of the Nuclear Hormone Receptor RORg in Transcriptional Regulation, Thymocyte Survival, and Lymphoid Organogenesis D.R. Littman, Z. Sun, D. Unutmaz, M.J. Sunshine, H.T. Petrie, and Y.-R. Zou    373 What Keeps a Resting T Cell Alive? C.B. Thompson, J.C. Rathmell, K.A. Frauwirth, T. Lindsten, C.M. Rudin, J.T. Opferman, P.G. Ashton-Rickardt, M.H. Harris, N.S. Chandel, P.T. Schumacker, and M.G. Vander Heiden    383

Cytokine Signaling and Responses

Differential Roles of Cytokine Signaling during T-cell Development R. Moriggl, J.-C. Marine, D.J. Topham, S. Teglund, V. Sexl, C. McKay, R. Piekorz, D. Wang, E. Parganas, A. Yoshimura, and J.N. Ihle    389 Negative Regulation of Cytokine Signaling by the SOCS Proteins N.A. Nicola, S.E. Nicholson, D. Metcalf, J.-G. Zhang, M. Baca, A. Farley, T.A. Willson, R. Starr, W. Alexander, and D.J. Hilton    397 IL-4 Signaling Is Regulated through the Recruitment of Phosphatases, Kinases, and SOCS Proteins to the Receptor Complex J. Losman, X.P. Chen, H. Jiang, P.-Y. Pan, M. Kashiwada, C. Giallourakis, S. Cowan, K. Foltenyi, and P. Rothman    405 Signaling via the IL-2 and IL-7 Receptors from the Membrane to the Nucleus W.J. Leonard, K. Imada, H. Nakajima, A. Puel, E. Soldaini, and S. John    417 Potential Roles of Stat1 and Stat3 in Cellular Transformation J.F. Bromberg and J.E. Darnell, Jr.    425 Innate Immune Induction of the Adaptive Immune Response R. Medzhitov and C.A. Janeway, Jr.    429 Attenuation of Tumor Necrosis Factor a Gene Transcription in Macrophages by an Autocrine Factor M. Baer, S. Nedospasov, and P.F. Johnson    437 Mechanism of Chromatin Recognition and Transcriptional Regulation by LEF-1 and the Wnt/Wg-responsive LEF-1:b-Catenin Complex A. Tutter, G.S. McAlpine, and K.A. Jones    445 HIV and SIV Nef Modulate Signal Transduction and Protein Sorting in T Cells J. Skowronski, M.E. Greenberg, M. Lock, R. Mariani, S. Salghetti, T. Swigut, and A.J. Iafrate    453 Transcription Factor IRF-1 and Its Family Members in the Regulation of Host Defense T. Taniguchi, N. Tanaka, K. Ogasawara, S. Taki, M. Sato, and A. Takaoka    465

NF-kB/NF-AT/TRAF

NF-kB Activation by Tumor Necrosis Factor and Interleukin-1 Z. Cao, M. Tanaka, C. Regnier, M. Rothe, A. Yamit-hezi, J.D. Woronicz, M.E. Fuentes, M.H. Durnin, S.A. Dalrymple, and D.V. Goeddel    473 Role of NF-kB in T-lymphocyte Development R.E. Voll and S. Ghosh    485 The IkB Kinase: A Master Regulator of NF-kB, Innate Immunity, and Epidermal Differentiation M. Delhase and M. Karin    491 Signaling through Calcium, Calcineurin, and NF-AT in Lymphocyte Activation and Development K. Stankunas, I.A. Graef, J.R. Neilson, S.-H. Park, and G.R. Crabtree    505 NF-AT5: The NF-AT Family of Transcription Factors Expands in a New Direction C. López- Rodríguez, J. Aramburu, A.S. Rakeman, N.G. Copeland, D.J. Gilbert, S. Thomas, C. Disteche, N.A. Jenkins, and A. Rao    517 Signal Integration by Transcription-factor Assemblies: Interactions of NFAT1 and AP-1 on the IL-2 Promoter L. Chen, A. Rao, and S.C. Harrison    527 Structure and Mechanism in NF-kB/IkB Signaling T. Huxford, S. Malek, and G. Ghosh    533 Structural Studies of Human TRAF2 H. Wu, Y.C. Park, H. Ye, and L. Tong    541 Structural and Biochemical Analysis of Signal Transduction by the TRAF Family of Adapter Proteins S.M. McWhirter, S.S. Pullen, B.G. Werneburg, M.E. Labadia, R.H. Ingraham, J.J. Crute, M.R. Kehry, and T. Alber    551

T-cell Differentiation

Molecular Basis of T-cell Differentiation R.A. Flavell, B. Li, C. Dong, H.-T. Lu, D.D. Yang, H. Enslen, C. Tournier, A. Whitmarsh, M. Wysk, D. Conze, M. Rincón, and R.J. Davis    563 Tissue-specific Regulation of Cytokine Gene Expression I.-C. Ho, J.I. Kim, S.J. Szabo, and L.H. Glimcher    573 Bi-stable Transcriptional Circuitry and GATA-3 Auto-activation in Th2 Commitment K.M. Murphy, W. Ouyang, S. Ranganath, and T.L. Murphy    585 Multiple Levels of Regulation of Th2 Cytokine Gene Expression N. Arai, H.J. Lee, I. Ferber, H. Kurata, and A. O'Garra    589 Bias in the Expression of IL-4 Alleles: The Use of T Cells from a GFP Knock-in Mouse C. Pannetier, J. Hu-Li, and W.E. Paul    599 Summary: Signals and Beyond R.A. Flavell    603