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Molecular Analysis of B Lymphocyte Development and Activation (Paperback, 2005 ed.)
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Molecular Analysis of B Lymphocyte Development and Activation (Paperback, 2005 ed.)
Series: Current Topics in Microbiology and Immunology, 290
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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...4
9 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*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 Schatz,D. G.
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