ｂ細(xì)胞和抗體bcell(參考版)
2024-10-06 20:53本頁(yè)面
【正文】 Junctional diversity IgH 1,000,000 ? 2,000 ? 1,200 [IgH (x) ? ] + [ IgH (x) ? ] [ 106 x 2 x 103 ] + [ 106 x x 103 ] 2x 109 + x 109 = x 109 V D J mature mRNA TRANSLATION AAAAAA V D J IgH CHAIN PROTEIN DRAWING THE REGIONS IN ~CORRECT PROPORTIONS V H C H REGION REGION IgH CHAIN U511C 。VE ANTIBODY REPERTOIRE: CREATING DIVERSITY IN BCR Sources of diversity: Combinatorial diversity V D J Combinations IgH 65 27 6 10,530 ? 40 5 200 ? 30 4 120 Junctional Combinations (x) diversity Product IgH ~10,000 100 1,000,000 ? 200 10 2,000 ? 120 10 1,200 CREATING THE NA207。ve + Adaptive Antigen QUESTION: How can the immune system deal with an almost endless number of antigens that it has never been exposed to previously? IMMUNE SYSTEM: Creates a “preexisting” Antibody Repertoire* prior to any antigen exposure REPERTOIRE = Sum total of the body’s different antibodies ~= 10 billion different antibodies CREATING THE NA207。ve) B cell** IgM IgD Na239。 IgD are identical: B cell is still “clonal” Na239。ve mature B CELL: IgM amp。 IgD mRNA of B cell includes ? constant region in addition to ? constant region mRNA: termed a “l(fā)ong nuclear transcript” mRNA alternative splicing results in either ? constant region or ? constant region with the same VDJ 3 VDJ IgH GENE VDJ nascent mRNA LONG NUCLEAR TRANSCRIPT U5161 TRANSCRIPTION THRU MU and DELTA TRANSLATION TRANSLATION VDJ VDJ VDJ AAAAAA VDJ MU CHAIN VDJ DELTA CHAIN ALTERNATIVE SPLICING OF IgH mRNA produces NA207。VE IMMATURE B CELL to NA207。 ? gene: chr. 22 Study V K J K C Kappa KAPPA GENE ORGANIZATION: KAPPA GENE REARRANGES before LAMBDA GENE EXONs Single EXON (single domain) N = 40 N = 5 V K J K C Kappa J K C K KAPPA GENE ORGANIZATION U5132 V K L V EXONs K K C K V K J K C V J REARRANGEMENT Kappa GENE Kappa GENE V K J K C K Kappa GENE ACTION OF RECOMBINASE KAPPA LIGHT CHAIN V to J REARRANGEMENT IRREVERSIBLE DNA EVENT: Small preB cell U5141 V 1 K J 3 K Deletional event TRANSLATION mature mRNA AAAAAAAAA U5142 nascent mRNA LIGHT CHAIN mRNA TRANSCRIPTION AND TRANSLATION V J K K C K Kappa GENE TRANSCRIPTION mRNA splicing VJC KAPPA IgL (LIGHT) CHAIN PROTEIN: U5151 VJ REARRANGEMENTS VJ, ALLELE A PRODUCTIVE NONPRODUCTIVE NAIVE IMMATURE B CELL DEVEL
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