免疫球蛋白4.pptx

Immunoglobulin GeneticsHistorySame C region could associate with many V regionsIgG Ab with different specificitiesSame V region could associate with many C regionsSame idiotype on IgG and IgM AbV and C regions coded for by separate genesLight Chain Gene FamiliesGerm line gene organizationJ1C1EJ2C2EJ3C3EJ4C4EPLV1PLVnPLV2Lambda light chain genes;n=30PLV 1PLV nPLV 2J 2J 3J 5C EJ 1J 4Kappa light chain genes;n=300Light Chain Gene FamiliesGene rearrangement and expressionLV 1LV nLV 2J 2 J 3J 5C J 1J 4DNAPPPEPPELV 1LJ 5C V 2J 4DNADNA RearrangementVCJVCProteinTransport to ERProteinTranslationCL V JELVCJRNATranscriptionPrimary transcriptCL V JRNA ProcessingRNAmRNAHeavy Chain Gene FamilyGerm line gene organizationIntrons separate exons coding for H chain domainsHeavy chain genes;Vn=1000,Dn=15PL V1PLVnPL V2D2 D3D1DnCCC3CC 2C 1C 4C1C2J2J3J5J1J4ECH1HCH2CH3CH4Heavy Chain Gene FamilyGene rearrangement and expressionPLV1PLVnPLV2D2 D3D1DnCCJ2J3J5J1J4EDJ rearrangementPLVnPLV1PLV2D2D1CCJ5J4EDNAVDJ rearrangementD2CCJ5J4EPLV1PLV2DNATranscriptionD2CCJ5J4ELV2RNAPrimary transcriptHeavy Chain Gene FamilyGene rearrangement and expressionEPrimary transcriptEJ4D2V2CCJ5LCCJ5LD2 J4V2RNA ProcessingAnmRNA for CCLDJVCLDJVAnmRNA for CTranslationC heavy chainCLDJVCLDJVC heavy chainTransport to ERC heavy chainVCCDJVCDJVC heavy chainVCMechanism of DNA RearrangementsRecombination signal sequences(RSS)NonmerHeptamer1 or 2 turn signals Rag-1 and Rag-2LV2JC1Lambda light chainsLV1JC2Kappa light chainsHeavy chainsLV2JC211D HeptamerCACAGTGGTGTCAC NonamerACAAAAACCTGTTTTTGG23 bp23 bpTwo turn RSS2 NonamerGGTTTTTGTCCAAAAACA HeptamerCACTGTGGTGACAC12 bp12 bpOne turn RSS1Order of Ig Gene Expression+-Heavy chain geneVDJ recombinationProductive rearrangement?YesNoTranscribe/translate1st2ndorApoptosisProgenitor B cellPre B cell()Heavy chainPaternalMaternalOrder of Ig Gene Expression+-Light chain geneVJ recombinationProductive rearrangement?YesNoTranscribe/translateLight chain4 thApoptosis1st -2nd-3rd-4th -orPre B cellMature B cell+Order of Ig Gene Expression Explains:Why an individual B cell only produces one kind of Ig with one kind of heavy and one kind of light chainWhy an individual B cell makes only makes antibodies of one specificityWhy there is allelic exclusionOrigin of Antibody DiversityHistoryDefinition Diversity(repitoire)is the total of all the Ab specificities that an organism is capable of expressingTheoriesGerm line theorySomatic mutation theoryOrigin of Antibody DiversityCurrent conceptsMultiple V genes V-J and V-D-J joining Junctional diversity N region insertions Amino acid sequences not encoded in the germ lineD regionTGGCCCPro TrpCCCC CCV geneTGGD regionCCCC CCV geneTGGCGGCCCPro ArgCCCC CCV geneTGGD regionCGCCCCPro Pro-GTCAATG-GTCAATG-+Break DNATdT adds nucleotidesLigateN region insertionIntronJDJJJDDDGeneration of N region insertionsOrigin of Antibody DiversityCurrent conceptsMultiple V genes V-J and V-D-J joining Junctional diversity N region insertions Somatic mutation Combinatorial association MultispecificityGeneration of Diversity Ag independent process Clonal selectionT Cell Antigen ReceptorHeterodimer of an and a chainGene structure and expression of the chain is analogous to the immunoglobulin heavy chainGene structure and expression of the chain is analogous to the immunoglobulin light chainNo somatic mutation in T cells