Ch5 - Content List for Chapter 5 Genetic Organization and...

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Content List for Chapter 5 Genetic Organization and Expression of Ig Genes Many V genes and limited C genes o V domain of 110 amino acids is encoded separately from C regions o Ag-binding occurs at V ends Functional expression requires rearrangement o No functional transcription or translation until the segments are rearranged to form an intact Ig gene Rearrangement is regulated with differentiation Rearrangement is a source of diversity Germline vs. somatic variation Germ line theory o A large repertoire of Ig is encoded in germline Somatic Variation Theory o A small number of Ig is encoded in the germline and the repertoire is generated by mutation or recombination Antibody protein structure predicts genetic structure Dryer and Bennett theory o Many V region genes and single genes for each C region class, subclass, type and subtype o Genes are joined by DNA recombination o Reasons Ab’s with identical V region protein sequences with both gamma and mu heavy chain C region sequences Ab’s with identical idiotypes but differing isotypes A rabbit heavy chain V region allotypic determinant associated with alpha, gamma, mu heavy chains (a rare instance allotype localized to V rather than C) Tonegawa experiment o First direct evidence that separate genes encode the V and C regions and genes are rearranged in the course of B-cell differentiation o Rearrangement of C gene deletes an extensive section of the germ line DNA thereby creating differences between rearranged and un-rearranged Ig in loci in the distribution and number of restriction sites o This results in the generation of different restriction patterns by rearranged and un- rearranged loci Detailed structure of Ig genes Kappa and lambda light chain families contain V, J, and C gene segments o Rearranged VJ segments encode the varaible region on light chains o The J segment (joining) encodes part of the V region but is associated with the C region
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Ch5 - Content List for Chapter 5 Genetic Organization and...

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