Medical Microbiology

combinationresultinginarearrangementofthesesegments,suchthat

oneVH,oneDH,andoneJHsegmentbecomecombined.Thusthegerm

linedoesnotcontainonegenegoverningthevariabledomain,butrather

genesegmentswhicheachencodefragmentsofthenecessaryinformation.

MatureBcellscontainafunctionalgenewhich,asaresultoftherecombina-

tionprocess,iscomprisedofoneVHDHJHsegment.ThediversityofT-cell

receptorsisgeneratedinasimilarmanner(seep. 5 7).

Fig.2. 4 explainstheprocessofgeneticrecombinationusingexamplesof

animmunoglobulinHchainandT-cellreceptorachain.

Themajorfactorsgoverningimmunoglobulindiversityinclude:

&MultipleVgenesegmentsencodedinthegermlines.

&TheprocessofVJ,andVDJ,geneticrecombination.

&Combinationoflightandheavychainproteinstructures.

&Randomerrorsoccurringduringtherecombinationprocess,andinclusion

ofadditionalnucleotides.

&Somaticpointmutations.

Intheory,thepotentialnumberofuniqueimmunoglobulinstructuresthat

couldbegeneratedbyacombinationoftheseprocessesexceeds 1012 ,how-

ever,thebiologicallyviableandfunctionalrangeofimmunoglobulinspecifi-

citiesislikelytonumbercloserto 104.

TheDifferentClassesofImmunoglobulins

Classswitching.Theprocessofgeneticrecombinationresultsinthegenera-

tionofafunctionalVDJgenelocatedonthechromosomeupstreamofthose

54 2 BasicPrinciplesofImmunology

Fig.2. 4 aHeavychainofhumanIgG.Thedesignationsforthegenesegments

inthevariablepartoftheHchainareV(variable),D(diversity),andJ(joining).

Thesegmentsdesignatedasl,d,c,a,andecodefortheconstantregion

anddeterminetheimmunoglobulinclass.TheVsegmentoccursinseveralhun-

dredversions,theDsegmentinoveradozen,andtheJsegmentinseveralforms.

V,D,andJsegmentscombinerandomlytoformasequence(VDJ)whichcodesfor

thevariablepartoftheHchain.ThisrearrangedDNAisthentranscribed,creating

theprimaryRNAtranscript.Thenon-codinginterveningsequences(introns)are

thensplicedout,andtheresultingmRNAistranslatedintotheproteinproduct.

bachainofmouseT-cellreceptor.VariousdifferentV,D,andJgenesegments

(forbandd),VandJgenesegments(foraandc)areavailablefortheT-cellre-

ceptorchains.TheDNAlociforthedchaingenesarelocatedbetweenthosefor

theachain. "

2

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Kayser, Medical Microbiology © 2005 Thieme

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