Medical Microbiology

Insummary,thenon-responsivenessofT-cellscanbeachievedby:negative
selectioninthethymus;byexcessiveinductionintheperiphery;orbyseque-
strationoftheantigenoutsidethelymphoidorgans.Persistenceoftheanti-
genwithinthelymphoidtissuesisaprerequisiteforthefirsttwomechan-
isms.Forthethirdmechanism,itistheabsenceofantigenwithinlymphatic
organswhichguaranteesnon-responsiveness.Thereisalsoanecessaryrole
for’second’-or’costimulatory’-signalsintheactivationofTcellswithinlym-
phoidtissues,however,theirroleinT-cellresponsivenesswithinsolidorgans
remainsunclear.

B-CellTolerance............................................

IncontrasttoclassiccentralT-celltolerance,Bcellscapableofrecognizing
self-antigensappearunlikelytobesubjectedtonegativeselection(Table

2. 7 ).B-cellregenerationinthebonemarrowisaveryintensiveprocess,dur-
   ingwhichantigenselectionprobablydoesnotplayanimportantrole.
   AlthoughnegativeselectionofbonemarrowBcellscanbedemonstratedex-
   perimentallyforhighly-expressedmembrane-boundMHCmolecules(in
   antibody-transgenicmice)—thisapparentlydoesnotoccurformorerare
   membrane-boundantigens,orformostsolubleself-antigens.Asageneral
   rule,thesepotentiallyself-reactiveBcellsarenotstimulatedtoproduce
   animmuneresponsebecausethenecessaryThelpercellsarenotpresent
   asaresultofhavingbeingsubjectedtonegativeselectioninthethymus.
   BcellandantibodytoleranceisthereforelargelyaresultofTcelltolerance
   whichresultsintheabsenceofThelp.
   Thefindingthatacertainantigenicstructuresandsequencescanactivate
   BcellsintheabsenceofThelpindicatesthatautoreactiveBcellswhichare
   presentcouldbepromptedtoproduceanIgMautoantibodyresponseviaIg
   cross-linkingbyparacrystallinemultimericantigens.However,sinceself-
   antigensarenotnormallyaccessibletoBcellsinsuchrepetitiveparacrystal-
   linepatterns,theinductionofIgMautoantibodyresponsesisnotnormally
   observed.ItisinterestingtonotethatDNAandcollagen,whichoftencon-
   tributetochronicautoantibodyresponses,exhibitrepetitiveantigenstruc-
   tures.ThesestructuresbecomeaccessibletoBcellswithininflamedlesions,
   andmaythereforeinduceautoantibodyresponsesincertaincircumstances.
   AchronicautoantibodyresponseoftheIgGtype,however,alwaysrequires
   Thelparisingfromthepresentationofself-peptidesbyMHCclassIImole-
   cules.Ignoredself-peptides,andinalllikelihoodinfectiousagents,mayplay
   aroleinprovidingsuchThelp.(ForinstanceKlebsiellaorYersiniainrheu-
   maticdiseases,Coxsackievirusinfectionsindiabetes,orotherchronicpara-
   siticinfections.)

ImmunologicalTolerance 93

2

All rights reserved. Usage subject to terms and conditions of license

Kayser, Medical Microbiology © 2005 Thieme

All rights reserved. Usage subject to terms and conditions of license.