Insights 2136 Monocytes find a new place to dwell in the niche of heartbreak hotel Bart N. Lambrecht and Martin Guilliams Perspectives 2137 Guidelines for genetic studies in single patients: lessons from primary immunodeficiencies Jean-Laurent Casanova, Mary Ellen Conley, Stephen J. Seligman, Laurent Abel, and Luigi D. Notarangelo THE JOURNAL OF EXPERIMENTAL MEDICINE VOLUME 211 NUMBER 11 OCTOBER 20, 2014 www.jem.org Brief Definitive Reports 2151 Progressive replacement of embryo-derived cardiac macrophages with age Kaaweh Molawi, Yochai Wolf, Prashanth K. Kandalla, Jeremy Favret, Nora Hagemeyer, Kathrin Frenzel, Alexander R. Pinto, Kay Klapproth, Sandrine Henri, Bernard Malissen, Hans-Reimer Rodewald, Nadia A. Rosenthal, Marc Bajenoff, Marco Prinz, Steffen Jung, and Michael H. Sieweke 2159 Immunoglobulin E plays an immunoregulatory role in lupus Barbara Dema, Nicolas Charles, Christophe Pellefigues, Tiffany K. Ricks, Ryo Suzuki, Chao Jiang, Jorg Scheffel, Sarfaraz Hasni, Victoria Hoffman, Mathieu Jablonski, Karim Sacré, Delphine Gobert, Thomas Papo, Eric Daugas, Steve Crampton, Silvia Bolland, and Juan Rivera Articles 2169 The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation Sebastian Carotta, Simon N. Willis, Jhagvaral Hasbold, Michael Inouye, Swee Heng Milon Pang, Dianne Emslie, Amanda Light, Michael Chopin, Wei Shi, Hongsheng Wang, Herbert C. Morse III, David M. Tarlinton, Lynn M. Corcoran, Philip D. Hodgkin, and Stephen L. Nutt 2183 The miR-155–PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation Dong Lu, Rinako Nakagawa, Sandra Lazzaro, Philipp Staudacher, Cei Abreu-Goodger, Tom Henley, Sara Boiani, Rebecca Leyland, Alison Galloway, Simon Andrews, Geoffrey Butcher, Stephen L. Nutt, Martin Turner, and Elena Vigorito 2199 The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells Bettina Grötsch, Sebastian Brachs, Christiane Lang, Julia Luther, Anja Derer, Ursula Schlötzer-Schrehardt, Aline Bozec, Simon Fillatreau, Ingolf Berberich, Elias Hobeika, Michael Reth, Erwin F. Wagner, Georg Schett, Dirk Mielenz, and Jean-Pierre David 2213 Myeloproliferative neoplasms can be initiated from a single hematopoietic stem cell expressing JAK2-V617F Pontus Lundberg, Hitoshi Takizawa, Lucia Kubovcakova, Guoji Guo, Hui Hao-Shen, Stephan Dirnhofer, Stuart H. Orkin, Markus G. Manz, and Radek C. Skoda ON THE COVER Articles from Carotta et al. and Lu et al. reveal the mechanisms and regulation of the transcription factor PU.1 in terminal B cell differentiation. The cover image depicts plasma cells secreting antibody in a lymph node. The image was created by Etsuko Uno and Drew Berry of the Walter and Eliza Hall Institute. See pages 2169 and 2183 2231 Genomic and bioinformatic profiling of mutational neoepitopes reveals new rules to predict anticancer immunogenicity Fei Duan, Jorge Duitama, Sahar Al Seesi, Cory M. Ayres, Steven A. Corcelli, Arpita P. Pawashe, Tatiana Blanchard, David McMahon, John Sidney, Alessandro Sette, Brian M. Baker, Ion I. Mandoiu, and Pramod K. Srivastava 2249 Regulation of YAP by mTOR and autophagy reveals a therapeutic target of tuberous sclerosis complex Ning Liang, Chi Zhang, Patricia Dill, Ganna Panasyuk, Delphine Pion, Vonda Koka, Morgan Gallazzini, Eric N. Olson, Hilaire Lam, Elizabeth P. Henske, Zheng Dong, Udayan Apte, Nicolas Pallet, Randy L. Johnson, Fabiola Terzi, David J. Kwiatkowski, Jean-Yves Scoazec, Guido Martignoni, and Mario Pende 2265 Myeloproliferative neoplasms can be initiated from an HSC expressing JAK2-V617F See page 2213 Specific fibroblastic niches in secondary lymphoid organs orchestrate distinct Notch-regulated immune responses Nicolas Fasnacht, Hsin-Ying Huang, Ute Koch, Stéphanie Favre, Floriane Auderset, Qian Chai, Lucas Onder, Sandra Kallert, Daniel D. Pinschewer, H. Robson MacDonald, Fabienne Tacchini-Cottier, Burkhard Ludewig, Sanjiv A. Luther, and Freddy Radtke 2281 microRNA-mediated regulation of mTOR complex components facilitates discrimination between activation and anergy in CD4 T cells Antoine Marcais, Rory Blevins, Johannes Graumann, Amelie Feytout, Gopuraja Dharmalingam, Thomas Carroll, Inês F. Amado, Ludovica Bruno, Keunwook Lee, Thierry Walzer, Matthias Mann, Antonio A. Freitas, Mark Boothby, Amanda G. Fisher, and Matthias Merkenschlager 2297 Spt5 accumulation at variable genes distinguishes somatic hypermutation in germinal center B cells from ex vivo– activated cells Robert W. Maul, Zheng Cao, Lakshmi Venkataraman, Carol A. Giorgetti, Joan L. Press, Yves Denizot, Hansen Du, Ranjan Sen, and Patricia J. Gearhart 2307 CARD9 mediates Dectin-1–induced ERK activation by linking Ras-GRF1 to H-Ras for antifungal immunity Xin-Ming Jia, Bing Tang, Le-Le Zhu, Yan-Hui Liu, Xue-Qiang Zhao, Sara Gorjestani, Yen-Michael S. Hsu, Long Yang, Jian-Hong Guan, Guo-Tong Xu, and Xin Lin Corrections 2323 The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells Bettina Grötsch, Sebastian Brachs, Christiane Lang, Julia Luther, Anja Derer, Ursula Schlötzer-Schrehardt, Aline Bozec, Simon Fillatreau, Ingolf Berberich, Elias Hobeika, Michael Reth, Erwin F. Wagner, Georg Schett, Dirk Mielenz, and Jean-Pierre David YAP is required for tumorigenesis of tuberous sclerosis complex See page 2249