Immunoglobin Gene Structure & BCR Gene

Immunoglobin Gene Structure: HIGHLY REGULATED! DNA segment w/ gene segments Veegmen 100-1 V.D.J segments 45 different v segments } 23 fandomly recombined together different D segments -going through a stage of development 6 different J segments NOT SPICING all possible genes are present UNTIL recombination occurs splicing: occurs after transcription to mRNA (NOE DNA) →after recombination, excess genes are degraded leader sequence signals exocytesis/secretion from cell membrane Cu (constant mu heavy chain) (IgM) constant region RSS (recognition signal sequences): conserved sequences of neti-coding DNA, that are adjacent to coding DIVA made up of 3 individual sequences: Heptamer (base pairs) RSS Heptamer Spacer 12/23 Nonamer Spacer Sequences (12/13 bp) Nonamer (9bp) EVERY SINGLE GENE SEGMENT CONTAINS A RSS! 12/23 rule recombination machinery is designed to pair one RSS bearing a 12 bp Spacer with another bearing a 13 bp Spacer →mechanism by which the cell ensures/promotes the correct pairing of gene segments RAG 1/2 are part of the complex that catalyzes the recombination of adjacent genes AAG 2 Enzyme Complex picks and recombines/assembles various gene segments inte segments of DNA that con be expressed How dres BAG / now which segments to choose? It doesn't! its chosen of RANDOM! defective MGsevate combined immunodefistry (example 30.10) BCR/Antibody Gene: light chains will always be EITHER kappa (k) or lambda (l) BUT NEVER both heavy chain, potential k, and potential l are happening on 3 seperate chromosomes My Child Igh igk اوا Light Chains Contain: 12 bp is essentially one turn in the Variable Regions Joining Regions Constant Regions No Diversity Regions so where do the 12 bp come from? double helix and 23 by is two turns Heavy Chains Contain Variable Regions the J region can have 12 bp in some situations Diversity Regions Joining Regions Constant Regions Allelic Exclusion and the Order of Ig Locus Rearrangement: The Problem each gene has 2 copies (1 from mom and 1 from dad) if they rearrange randomly and independently, how does each cell have only one specificity? (and not 2 sne for each allele) The solution allelic exclusion turns off one allele one successful in-Frame heavy chain rearrangement has been made the same is true for in and A light rearrangement at the offer heary chain lacus stops and that allele is no longer expressed chain lact each B-cell will matte only ONE Functional heavy chain re arrangement and only ONE functimal light chain rearrangement THUS each B-cell produces antibodies with only a single variable region single specificity single epitope tecognized ch 35 13 cach cell develops one specificity 50 it only happens once per cell BUT cach cell generates a different specificity. the Igh locus is marranged before lyl if the Igh