Medical Microbiology

resultinerrors,oreventheactivationofoncogenes.Theresultsofthisprocess
maythereforeincludethegenerationofB-celllymphomasandleukemia’s.
Sincetheoriginalerroroccursinasinglecell,suchtumorsaremonoclonal.
UncontrolledproliferationofdifferentiatedBcells(plasmacells)resultsin
thegenerationofmonoclonalplasmacelltumorsknownasmultiplemye-
lomas or plasmocytomas. Occasionally, myelomas produce excessive
amountsofthelightchainsofthemonoclonalimmunoglobulin,andthese
proteinscanthenbedetectedintheurineasBence-Jonesproteins.Such
proteinsrepresentedsomeofthefirstimmunoglobulincomponentsacces-
sibleforchemicalanalysisandtheyrevealedimportantearlydetailsregard-
ingimmunoglobulinstructure.

MonoclonalAntibodies.................................

Anormalimmuneresponseusuallyinvolvestheresponseandproliferationof
numerousBcellclones,bearingABSwithvaryingdegreesofspecificityfor
thedifferentepitopescontainedwithintheantigen.Thustheimmunere-
sponseisnormallypolyclonal.Itispossibletoisolateasinglecellfrom
suchapolyclonalimmuneresponseinanexperimentalsetting.Fusing
thiscellwithan“immortal”proliferatingmyelomacellresultsingeneration
ofahybridoma,whichthenproduceschemicallyuniformimmunoglobulins
oftheoriginalspecificity,andinwhateveramountsarerequired.Thismethod
wasdevelopedbyKoelerandMilsteinin 19 75,andisusedtoproducemono-
clonalantibodies(Fig.2. 10 ),whichrepresentimportanttoolsforexperimen-
talimmunology,diagnostics,andtherapeutics.Manymonoclonalantibodies
arestillproducedinmouseandratcells,makingthemxenogeneicforhu-
mans.Attemptstoavoidtheresultingrejectionproblemshaveinvolved
theproductionofantibodiesbyhumancells(whichremainsdifficult),or
the“humanization”ofmurineantibodiesbyrecombinantinsertionofthe
variabledomainsofamurineantibodyadjacenttotheconstantdomains
ofahumanantibody.Thegenerationofatransgenicmice,inwhichtheIg
geneshavebeenreplacedbyhumangenes,hasmadetheproductionofhy-
bridoma’sproducingcompletelyhumanantibodiespossible.

T-IndependentBCellResponses.......................

BcellsrecognizeantigensviatheIgreceptor.However,iftheantigenisina
monomeric,oroligomeric,solubleformtheBcellcanonlymountaresponse
ifitundergoestheprocessofT-Bcollaboration.Manyinfectiouspathogens
carrysurfaceantigenswithpolyclonalactivationproperties(e.g.,lipopoly-
saccharide[LPS])and/orcrystal-likeidenticaldeterminants,whichareoften

ImmuneResponsesandEffectorMechanisms 69

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Kayser, Medical Microbiology © 2005 Thieme