MCB13 - DNA rearrangements that are intentionally variable,...

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Antibodies (Ig or Immunoglobulin molecules) are made by B cells. Each B cell makes one sequence of heavy chain and one sequence of light chain. Two subunits of each type become disulfide bonded together. The ‘variable domains’ of the light and heavy chains form binding sites for antigen . A pre-B cell must undergo large-scale genome rearrangements to generate functional light and heavy chain genes. Each B cell produces one antibody sequence, but different B cells make different antibody sequences because the process is intentionally variable and sloppy. DNA rearrangements that are intentionally variable, sloppy, and mutagenic provide us with the evolutionary advantage of adaptive immunity. 1 antigen binding site antigen binding site
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DNA deletion brings together gene segments to encode one light chain (V-J-C segments) and one heavy chain (V-D-J-C segments). Each V, D, or J segment has alternative copies; C is constant and added by mRNA splicing (covered later in the class). To make a light chain, one V segment is joined with one J segment: To make a heavy chain, one V joins one D joins one J segment: (In a mechanism that we won’t cover in this class, as soon as one proper light chain or heavy chain is expressed, additional genomic rearrangements are prevented.) V(D)J recombination 2
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DNA breakage and joining by the RAG recombinase The signal sequences for V(D)J recombination are imperfect inverted
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MCB13 - DNA rearrangements that are intentionally variable,...

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