The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.

The major histocompatibility complex (Mhc) is one of the few identified gene systems in domestic animals that is associated with quantitative traits such as disease resistance, immune response, growth, and reproduction. As knowledge of this important system increases, we move closer toward the reality of genetic enhancement of animal welfare and production efficiency. This book represents the current state of knowledge on the Mhc of agriculturally important animals and explores the latest advances in technology. For the first time, the unique findings of recent Mhc research are presented in a single source. The Major Histocompatibility Complex Region of Domestic Animal Species begins with a discussion of the evolution of Mhc. The chapters are then organized with respect to specific species, with a chapter devoted to each. The Mhc of mice and humans are used as a common reference for comparisons between diverse species. The text concludes with a look at future strategies and directions in Mhc research. Comparative immunologists and geneticists, veterinarians, animal breeders, researchers, and university and postgraduate students will all benefit from this detailed look at the evolution, structure, and organization of Mhc.

A comprehensive guide to the HLA (Human Leukocyte Antigen) system for immunologists and clinicians, this book contains up-to-date information on the MHC (Major Histocompatibility Complex) and its role in the immune response and in various diseases. The book explores the biological significance and role of the HLA system in organ and haematopoietic stem cell transplantation management. This volume is an invaluable guide to the full spectrum of HLA-related science while also serving as a conceptual and technical resource for those involved in HLA-related research and in clinical or surgical practice. In addition, it will be a primary point of contact for individuals working in other areas who suddenly find that their research is drawing them into the complexities of HLA genetics.

TheBlymphocytelineagerepresentsaleadingsystemforexploring- lecularmechanismsthatunderliecellfatespecification, differentiationand cellular activation. In the past five years major advances have been achievedintheanalysisofearlyBcelldevelopment, AIDdependentclass switchrecombinationaswellassomatichypermutationandBlimp-1re- latedplasmacelldifferentiation. Manyofthesefindingsandtheirimpli- tionsarecoveredinthisvolume. Twoemergentareasofresearchthatare includedinthecontributionsfocusonthepre-BCRandIkaros-familyp- teins. Thepre-BCRisanunusualmoleculardevicethatisusedtoexecute acriticaldevelopmentalcheckpointintheBlineage. Itsmechanismof- tion in relationto the pre-TCR and the mature antigen receptors (BCR, TCR)isofconsiderableinterest. Ikaros-familyproteinsappeartofunction viarecruitingtargetgenestodomainsofcentromericheterochromatinin the nucleus. Initially discovered in lymphocytes, they represent a novel system of gene regulationvia nuclearcompartmentalization. Finally, the volumeincludesachapteronWntsignalinginlymphopoiesis. Analysisof thisevolutionallyconservedpathwaywhichregulatescellularproliferation anddifferentiationindiversedevelopmentalcontextsbenefitedenormo- lyfromthediscoveryoftheLEF/TCFfamilyoffactorsinlymphocyticl- eages. ThisvolumeisdedicatedtothememoryofEugeniaSpanopoulou, ac- leagueandahighlyvaluedmemberofourscientificcommunity. Itc- tainsachapteronthebiochemistryofV(D)JrecombinationthatEugenia co-authoredwithDavidSchatz. Obituary Eugenia Spanopoulou was an extraordinary person and scientist. Her enormousintelligenceandenergysparkedimportantscientificdiscoveries, andvaultedhertoapointofbreathtakingpotential apotentialabruptly erasedattheageof37withthecrashofSwissairflight111onSeptember 3,1998. Lostwithherwereherhusband, AndrewHodtsev, andyoungson, Platon. Eugeniawaspassionatelyinterestedinunderstandingthemolecular- sisofdevelopmentandchoseashermodelsystemthedevelopmentofB andTlymphocytes. Shebeganbystudyingthetranscriptionalregulation oftheTcell-specificgene, Thy-1, asagraduatestudentinFrankGrosveld s labatMillHill, London. Thereafter, sheturnedherattentiontothetopicof V(D)Jrecombination, firstasapostdoctoralfellowwithDavidBaltimore attheWhiteheadInstituteinCambridge, Massachusettsandsubsequently inherownlaboratoryatMountSinaiSchoolofMedicineinNewYorkCity. Eugeniamadefundamentaldiscoveriesconcerningthebiochemicalme- anismofthisreaction, andhowdefectsinitscentralenzymaticcom- nents, RAG1andRAG2, canleadtoahumanseverecombinedimmuno- ficiencydisorder, knownasOmennsyndrome. Atthetimeof herdeath, shehadbeenaHowardHughesMedicalInstituteinvestigatorforlessthan ayear, buthadalreadyassembledalaboratoryof15peopleworkingonan extensivearrayoftopicsinearlylymphocytedevelopmentandV(D)J- combination. Eugenialivedeachmomentofherlifewithanintensityfittingforthe cityinwhichshelived. LikeManhattan, shesleptlittle. Sheexpectedagreat dealofherself, andonlyalittlelessfromthosewithwhomsheworked. - geniaalsohadhighexpectationsforthescientificprocessandwasouts- keninherpraiseorcondemnationofthosewhometorfellshortofthose expectations. Shewasquicktoformanopinionanddevotedherselffe- ciouslytofriendshipsandhypotheses. PerhapsthegreatesttestimonytoEugeniaistheaffectionandreverence feltforherby themembersof herlab. Whilethisstemmedinnosmall partfrompredictablesources herkeenmindandbroadknowledge it founditsdeepestsourceinEugenia sabilitytotransmit, byexampleand word, her love of a life of learning and exploration. SandroSantigata, a graduatestudentinEugenia slab, capturedthiseloquentlyatthememorial serviceforEugeniaandAndrew, whenhesaid: VIII Obituary Ifyouhaveeverbeenspellboundbyagreatstatue, enrapturedbyits strengthandvitality, enthralledbyitspurity, purposeandgraceandupli- edbythesenseofhopethatitsparkswithinyoursoul, thenyouhave- readyunderstoodwhyIadoredEugenia. Shesimplyembodiedtheideal- ticprinciplesthatformthecoreofadedicatedgraduatestudent sheart. Andtoseethesevaluesmaterializedintheformofone smentorcanbe nothingshortofinspirational. ListofContents GeneRegulatoryNetworksOrchestratingBCellFateSpecification, Commitment, andDifferentiation K. L. Medina.H. Singh. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Helix-Loop-HelixProteinsinLymphocyteLineageDetermination B. L. Kee. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Ikaros-FamilyProteins: InSearchofMolecularFunctions DuringLymphocyteDevelopment B. S. Cobb.S. T. Smale. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 BiochemistryofV(D)JRecombination y D. G. Schatz.E. Spanopoulou. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Thepre-BcellReceptorinBCellDevelopment: RecentAdvances, PersistentQuestionsandConservedMechanisms M. R. Clark.A. B. Cooper.L. D. Wang.I. Aifantis. . . . . . . . . . . . . . . . . 87 TranscriptionalControlofBCellActivation L. M. Corcoran . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 ExpressionofMHCIIGenes G. Drozina.J. Kohoutek.N. Jabrane-Ferrat.B. M. Peterlin. . . . . . . . . 147 ClassSwitchRecombination: AnEmergingMechanism A. L. Kenter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 Blimp-1;ImmunoglobulinSecretion andtheSwitchtoPlasmaCells R. Sciammas.M. M. Davis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 WntSignalinginLymphopoiesis A. Timm.R. Grosschedl. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 SubjectIndex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253 ListofContributors (Theiraddressescanbefoundatthebeginningoftheirrespectivechapters. ) Aifantis, I. 87 Kohoutek, J. 147 Clark, M. R. 87 Medina, K. L. 1 Cobb, B. S. 29 Peterlin, B. M. 147 Cooper, A. B. 87

This work is a natural history of the major histocompatibility complex written for anyone who is working on the MHC but wants to step back and review the complex in its entirety; for anyone who wants to be introduced to the MHC; or for anyone who is just curious about this much talked-about chromosomal region. By natural history is meant an all encompassing treatment of the MHC, both human and mouse, in its entire range and its details - but presented in a way that anybody can understand without consulting a variety of other sources. Most of the details are summarized in the form of tables whereas the text concentrates on generalizations and discussions. Thus, the book will be of interest to immunologists and geneticists seeking an overview of the subject and to graduate students in these disciplines. It will also be of value to technicians working in HLA-typing laboratories.

With this book we· want to address young graduate students, clini cians involved in transplantation, and technicians in transplantation immunology laboratories. The volume should give a comprehensive but basic, up to date introduction to the structure, function, and clinical importance of the HLA system. We believe that there is a need for such a survey, and think that the present level of our knowledge is an optimal occasion for publication. A significant number of ques tions have now been resolved, and our knowledge has reached a level of sophistication that provides the basis for additional questions and answers. Although the emphasis of this book is on the role of HLA anti gens in clinical transplantation, their involvement in other clinical contexts is also discussed. The main focus is on the human MHC an tigenic system, but MHC systems in other species are described as they contribute to our understanding of the structural and functional characteristics of HLA antigens. Some important issues related to laboratory techniques are also covered. The contributors have a close affiliation to the field of transplan tation immunology. A majority have even been playing important roles in unraveling the HLA system and its functions. We believe this has contributed significantly to the quality and clinical and practical relevance of the book. As editors, we drew up the principal guidelines and took care that the chapters can be read as separate entities, although this invariably results in some overlapping.