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This meeting took place in 2012

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Mutations, Malignancy and Memory - Antibodies and Immunity (C6)

Organizer(s) F. Nina Papavasiliou and Sebastian D. Fugmann
March 18—22, 2012
Boston Park Plaza • Boston, MA USA
Abstract Deadline: Nov 15, 2011
Late Abstract Deadline: Dec 15, 2011
Scholarship Deadline: Nov 15, 2011
Early Registration Deadline: Jan 17, 2012

Supported by an educational donation provided by Amgen

Summary of Meeting:
Mutations in the human genome are regarded as potentially disastrous events that lead to carcinogenesis. From the vantage point of B cell immunology, however, programmed DNA alterations at the antibody gene loci are essential for efficient antibody responses. A plethora of recent findings are beginning to illuminate open questions about the precise molecular mechanisms of these diversification processes, their regulation, and how errors in these pathways lead to cancer. Furthermore, the very same class of mutator enzymes plays an underappreciated role in non-lymphoid cancers, in antiviral responses and in epigenetic reprogramming. Antibody diversification not only shapes the repertoires of the immunological memory, but also those of auto-antibodies. The Keystone Symposia meeting on Mutations, Malignancy and Memory – Antibodies and Immunity will provide both a platform to integrate these more or less isolated fields and an opportunity to identify interfaces that could be relevant for therapeutic approaches in malignancies and autoimmune diseases.

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Conference Program    Print  |   View meeting in 12 hr (am/pm) time



Imperial Check Room

Plaza Ballroom
Welcome and Keynote Address

Imperial Ballroom
* F. Nina Papavasiliou, Deutsches Krebsforschungszentrum, Germany

Michel C. Nussenzweig, HHMI/Rockefeller University, USA
AID in Antibody Diversity and Lymphomas



Plaza Ballroom
Poster Setup

Plaza Ballroom
Poster Viewing

Plaza Ballroom
Generation of Diversity
This session focuses on the initiation of the antibody gene diversification event, V(D)J recombination, somatic hypermutation (SHM), class switch recombination (CSR), and immunoglobulin gene conversion(GCV), the key enzymes in these processes, AID and RAG1/2, and their regulation.

Imperial Ballroom
* David G. Schatz, Yale University School of Medicine, USA

Marjorie A. Oettinger, Massachusetts General Hospital, USA
V(D)J Recombination and Epigenetics

Tasuku Honjo, Kyoto University Graduate School of Medicine, Japan
Short Talk: An Evolutionary View of the Mechanism for the Immune and Genome Diversity

Javier M. Di Noia, Institut de Recherches Cliniques de Montreal, Canada
Regulation of AID

Ali A. Zarrin, Genentech, Inc., USA
Modifications of Endogenous Switch Regions Provide Novel Insights into the Mechanisms of AID Targeting and Class Switch Recombination

Sebastian D. Fugmann, Chang Gung University, Taiwan
Targeting AID-Dependent Diversification Processes to Antibody Genes

Heinz Jacobs, Netherlands Cancer Institute, Netherlands
Short Talk: Targeting of AID: Distinguishing between Accessibility and Binding

Patricia J. Gearhart, NIA, National Institutes of Health, USA
Short Talk: Transcriptional Stalling of RNA Polymerase II Gives AID Access to Immunoglobulin Variable Regions

Coffee Break

Imperial Foyer

Plaza Ballroom
Poster Session 1

Plaza Ballroom
Workshop 1: CSR/SHM/GCV Regulation and Targeting

Imperial Ballroom
* Claude-Agnès Reynaud, Necker-Paris Medical School, France

Nobuo Sakaguchi, Kumamoto University, Japan
Role of GANP in Transcriptional Regulation of Immunoglobulin Gene Locus

Amy L. Kenter, University of Illinois College of Medicine, USA
The Igh gamma1 Locus Organizes Long Range Chromatin Looping and Modulates CSR at Other CH Isotypes

Michel C. Cogné, Centre National de la Recherche Scientifique, France
Immunoglobulin Heavy Chain Locus Suicide Recombination in Mature B Cells

Mani Larijani, Memorial University of Newfoundland, Canada
Differences in the Enzymatic Efficiency of Human and Bony Fish AID are Mediated by a Single Residue in the C-Terminus Modulating Single-Stranded DNA Binding

Prashant Kodgire, University of Chicago, USA
Nucleosome Stability Dramatically Impacts the Targeting of Somatic Hypermutations

Jahan-Yar Parsa, University of Toronto, Canada
Negative Supercoiling Creates Single-Stranded Patches of DNA that are Substrates for AID-Mediated Mutagenesis

Minghui He, Stockholm University, Sweden
Cell Cycle Regulation of Ig Class Switching

Cesare Sala, Istituto Toscano Tumori, Italy
Activity of AID Driven by Cell Cycle Specific Promoters

Coffee Available

Imperial Foyer
DNA Repair and Genomic Instability
This session focuses on DNA repair in particular in the context of AID mediated sequence diversification reactions.

Imperial Ballroom
* Anne Durandy, Institut Imagine, France

Janet M. Stavnezer, University of Massachusetts Medical School, USA
AID-Induced DNA Breaks and their Repair during Class Switching

Kevin D. Mills, The Jackson Laboratory, USA
Widespread Genomic Breaks Generated by AID Are Prevented by Homologous Recombination

Jayanta Chaudhuri, Memorial Sloan Kettering Cancer Center, USA
Regulation of Immunoglobulin Class Switch Recombination

Peter M. Bowers, AnaptysBio, Inc., USA
Short Talk: Human Activation-Induced Cytidine Deaminase (AID) Activity is Similar in vivo and in vitro as Analyzed by Next-Generation Sequencing

On Own for Dinner



Plaza Ballroom
Poster Setup

Plaza Ballroom
Poster Viewing

Plaza Ballroom
B Cell Lymphomas - Mutations, Translocations and Transcription
This session focuses on mechanisms of B lymphoma formation linked to antibody gene diversification processes.

Imperial Ballroom
* Michael L. Atchison, University of Pennsylvania, School of Veterinary Medicine, USA

Markus Müschen, Beckman Research Institute, USA
Infectious Origins of Childhood Leukemia

Qiang Pan-Hammarström, Karolinska Institutet, Sweden
Pathway Targeted Deep-Sequencing of DNA-Repair Genes in Human B-Cell Lymphomas

Frederick W. Alt, Boston Children's Hospital, USA
Mechanisms Contributing to Genomic Rearrangements in B Lineage Cells

Alexander L. Kovalchuk, NIAID, National Institutes of Health, USA
Short Talk: A Mouse Model of Endemic Burkitt Translocations Reveals the Long-Range Boundaries of Ig-Mediated Oncogene Deregulation

Jane A. Skok, New York University School of Medicine, USA
Short Talk: Chromosomal Domains in Close Proximity to Igh in the Nucleus of Class Switching B Cells Are Predisposed to AID Mediated Translocations

Sophia Shalhout, Wayne State University, USA
Short Talk: Uracils in Genomic DNA: A Useful Marker for Studying Lymphomogenesis

Uttiya Basu, , USA
Short Talk: Co-Transcriptional Regulation of the B Cell Mutator Activation Induced Cytidine Deaminase by the Non-Coding RNA Surveillance Complex RNA Exosome

Coffee Break

Imperial Foyer

Plaza Ballroom
Poster Session 2

Plaza Ballroom
Workshop 2: Molecular Mechanisms of CSR and SHM

Imperial Ballroom
* Michel C. Cogné, Centre National de la Recherche Scientifique, France

Shyam Unniraman, Duke University, USA
Origin of Microhomologies during Class Switch Recombination

Ramiro E. Verdun, University of Miami, USA
The Classical NHEJ and the Alternative End-Joining Pathways are not Competing for the Processing of DNA Breaks during Class-Switch Recombination

Anne Durandy, Institut Imagine, France
Role of Mismatch Repair in Human Antibody Maturation

Richard Chahwan, Albert Einstein College of Medicine, USA
Coordinating DNA Mismatches and Double-Strand Breaks at the Immunoglobulin Gene

Huseyin Saribasak, Sifa University, Turkey
DNA Polymerase zeta Generates Tandem Mutations in Immunoglobulin Variable Regions

Catarina S. Cortesão, Instituto Gulbenkian de Ciência, Portugal
AID Does Not Affect the Global Frequency of Meiotic Recombination in Mice

Almudena R. Ramiro, Centro Nacional de Investigaciones Cardiovasculares, Spain
UNG Shapes the Specificity of AID-Induced Somatic Hypermutation

Svend Petersen-Mahrt, IFOM-Fondazione Istituto FIRC di Oncologia Molecolare, Italy
Pre- and Post-Lesion AID Complexes

Coffee Available

Imperial Foyer
Mutator Enzymes in B Cells and Beyond
This session focuses on non-classical roles of AID as a DNA demethylase as well as the biological function of other APOBEC deaminases (APOBEC2, APOBEC1, APOBEC3).

Imperial Ballroom
* Silvestro Conticello, ISPRO, Italy

Cristina Rada, MRC Laboratory of Molecular Biology, UK
AID and Other APOBEC Proteins

Simon Wain-Hobson, Institut Pasteur, France
The Human APOBEC3 Cluster of Viral DNA Mutators, Part of a Much Bigger Picture

Sébastien Landry, The Salk Institute, USA
Short Talk: APOBEC3A Expression Activates the DNA Damage Response and Induces Cell Cycle Arrest

F. Nina Papavasiliou, Deutsches Krebsforschungszentrum, Germany
The RNA Editor APOBEC1 Can Reprogram Gene Expression

Duane R. Wesemann, Harvard Medical School, USA
Short Talk: Inhibiting DNA Methylation to Reprogram Activated, IgH Isotype Switched B Cells to Functional Grade Induced Pluripotent Stem Cells

On Own for Dinner



Plaza Ballroom
Autoimmunity and Antibody Diversity
This session focuses on immunoglobulin diversification as a driver and/or guardian of autoimmune disease.

Imperial Ballroom
* Eric Meffre, Yale University School of Medicine, USA
AID is Required for B Cell Tolerance in Humans

Qing C. Chen, University of Maryland School of Medicine, USA
Low-Affinity Natural Autoantibodies Protect from Autoimmune Disease

Marilyn Diaz, NIEHS, National Institutes of Health, USA
The Role of AID in B-Cell Mediated Autoimmune Disease

Lawrence J. Wysocki, National Jewish Health, USA
AID Generates Anti-Nuclear Antibodies in Systemic Autoimmunity

Elisa Corsiero, Barts and the London School of Medicine, UK
Short Talk: Analysis of Recombinant Monoclonal Antibodies from Single B Cells Reveals Early Defects of B Cell Tolerance Checkpoints in Patients with Sjögren’s Syndrome

Benjamin Umiker, Merck, Co., Inc, USA
Short Talk: Aicda Expression in Immature B Cells as a Potential Mechanism for Tolerance and Autoantibody Production in a Model of Systemic Lupus Erythematosus (SLE)

Coffee Break

Imperial Foyer
On Own for Lunch and Recreation

Workshop 3: Deaminases and Tumorigenesis

Imperial Ballroom
* Kevin M. McBride, University of Texas MD Anderson Cancer Center, USA

Rahul M. Kohli, University of Pennsylvania, USA
AID/APOBEC Deaminases Discriminate against 5-Substituted Cytosines: Implications for DNA Demethylation

Silvestro Conticello, ISPRO, Italy
APOBEC1 and Mutagenesis

Denise P. Muñoz, Children's Hospital Oakland Research Institute, USA
Activation-Induced Cytidine Deaminase (AID) is Necessary for the Epithelial-Mesenchymal Transition (EMT) in a Breast Cancer Model

Saravanan Yuvaraj, Erasmus Medical Centrum, Netherlands
The Role of Antigenic Stimulation in the Pathogenesis of Chronic Lymphocytic Leukemia

Andrea Paun, National Institutes of Health, USA
Exploring the Contribution of NF-kappa B to the Establishment of B Cell Malignancies

Frederic B. Davi, Hôpital de la Pitié Salpêtrière Paris, France
Primary Intraocular Lymphomas Display a Remarkably Biased Immunoglobulin Heavy Chain Gene Repertoire and Precisely Targeted Somatic Hypermutation Suggesting Antigenic Selection of the Neoplastic Cells

Lesley Ann Sutton, Karolinska Institutet, Sweden
Transcriptome Sequencing Reveals Novel Mutations and Differential Gene Expression in Stereotyped Subsets of Chronic Lymphocytic Leukemia

Parameswary A. Muniandy, Beth Israel Deaconess Medical Center, Harvard Medical School, USA
Integrated Analysis of Tumor Transcriptome and miRNOME of B Cell Lymphoma Reveal Interplay of Multiple Cancer Signaling Pathways

Coffee Available

Imperial Foyer
Generation of B Cell Memory
This session focuses on the studies on the generation and maintenance of B cell memory and their antibody repertoire.

Imperial Ballroom
* Sebastian D. Fugmann, Chang Gung University, Taiwan

Antonio Lanzavecchia, Vir Biotechnology, Inc., USA
Antibody Repertoire in Memory B Cells

Patrick C. Wilson, University of Chicago, USA
Human B Cell Responses to Influenza; Lessons from Unique Populations

Mary M. Tomayko, Yale University School of Medicine, USA
Molecular Basis of B Cell Memory Generation and Maintenance

Alaitz Aranburu, Research Centre, Ospedale Bambino Gesu, Italy
Short Talk: The Defined Molecular Features of Adult IgM Memory B Cells Are “Imprinted” in the First Year of Life

Social Hour with Lite Bites

Plaza Ballroom

Plaza Ballroom



*Session Chair †Invited, not yet responded.

We gratefully acknowledge support for this conference from:

Directors' Fund

These generous unrestricted gifts allow our Directors to schedule meetings in a wide variety of important areas, many of which are in the early stages of research.

Click here to view all of the donors who support the Directors' Fund.

Keystone Symposia thanks our Sponsor(s) for generously supporting this meeting:

Educational donation provided by Amgen

We gratefully acknowledge the generous grant for this conference provided by:

National Institutes of Health

Grant No. 1R13AI098260-01

The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.

We gratefully acknowledge additional in-kind support for this conference from those foregoing speaker expense reimbursements:

Genentech, Inc.

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