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Unformatted text preview: Lecture 18 1 Bio Sci 104 Winter 2010 The Immune system II (many detailed contents that I did not mention in class were FYI only) IV. What is the basis of B cell antibody diversity, by which antibodies to virtually any antigen can be created? A. It is estimated that even before antigen stimulation, a mammal can synthesize at least 10 15 different antibody molecules. This diversity ensures that there will be an antibody (indeed, several antibodies) able to bind almost any antigen. How is this diversity created? At several levels: 1. There are multiple genes encoding different antibody variable regions . 2. These light and heavy chain genes are expressed independently in each individual B cell, and both L and H chains contribute to a portion of the antigen binding pocket. Thus different light and heavy chains can associate with one another , generating by combination millions more possible antigen binding pockets. 3. In addition, there is considerable flexibility in the manner in which the different variable sequences are pieced together into the final antibody , and additional somatic mutation can take place, which completes the generation of the necessary diversity. B. How are antibody genes and proteins assembled during B cell development? 1. Each type of Ig chain (light or heavy) is assembled from different gene segment pools. 2. Each pool contains a large number of (DNA) segments encoding different Variable- regions, but a much smaller number of segments encoding the C region. In mouse and humans: two pools of Variable-regions for assembling coding regions of the light chain: kappa and lambda (two main classes of the light chain constant regions). Only one pool of Variable region for assembling the coding sequences of the heavy chain. The very 3’ end of this variable region is linked to a segment encoding all five main classes of heavy chain constant regions (alpha, gamma, delta, mu and epsilon). (FYI) 3. General example : assembly of kappa light chains : a. hundreds of different possible V kappa coding segments, four possible J kappa (joint) segments, and one C kappa region on chromosome in fertilized zygote. b. in each B cell during development, one of these V kappa DNA segments is rearranged and joined to one of the J kappa DNA segments by a specific DNA recombinase. Intervening V kappa and J kappa segments that were not used are lost from genome of that B cell. Thus, by the time B cell development is over, each B cell contains its own unique V/J kappa fusion. Lecture 18 2 c. After this fusion occurs, the new V/J kappa fusion gene is transcribed by RNA polymerase together with the more 3' C kappa region. Any intervening J kappa segments remaining and other introns are spliced out, thus generating an mRNA joining a unique set of V/J/C kappa regions together....
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This note was uploaded on 03/15/2010 for the course BIS 104 taught by Professor Scholey during the Fall '08 term at UC Davis.
- Fall '08