【正文】
n 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 MATURE B CELL U5171 IgM plus L CHAIN IgD plus L CHAIN PROTEIN VDJ AAAAAA SPLICING RNA IgH ?chain IgL expression IgM expression Na239。ve mature B CELL: IgM amp。 IgD EXPRESSION IgH ? chain IgD expression Antigenbinding sites of IgM amp。 IgD are identical: B cell is still “clonal” Na239。ve Antibody Repertoire Mature (na239。ve) B cell** IgM IgD Na239。ve Antibody Repertoire Adaptive Antibody Repertoire “ Total” Antibody Repertoire = Na239。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 ANTIBODY REPERTOIRE: CREATING DIVERSITY IN BCR Sources of diversity: V D J Different VH’s, DH’s, JH’s IgH 65 27 6 VL’s, JL’s ? 40 5 ? 30 4 Variations in junctions* Chain Junctions Incr. diversity Imprecise rebination IgH 2 100 Nregion diversity IgL 1 10 Various binations of IgH and IgL * 10 fold incr. diversity with each junction CREATING THE NA207。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 ANTIBODY REPERTOIRE: CREATING DIVERSITY IN BCR Combinatorial amp。 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