Gene Rearrangement

A primary mechanism for generating a wide variety of different antibodies using a limited-size region of DNA uses a strategy similar to that of a savvy but well-dressed traveler living out of a small suitcase. By mixing and matching different shirts, pants, and shoes, the traveler can create a wide variety of unique outfits from a limited number of components. Likewise, the maturing B cell selects three gene segments, one each from DNA regions called V (variable), D (diversity), and J (joining), to form an ensemble that encodes a nearly unique variable region of the heavy chain of an antibody (figure 16.22).

A human lymphoid stem cell has about 65 different V segments, 27 different D segments, and 6 different J segments in the DNA that encodes the variable region of the heavy chain. As a B cell develops, however, two large regions of DNA are permanently removed, effectively joining discrete V, D, and J regions. The joined segments encode the antibody that the mature B cell is programmed to make. Thus, one B cell could express the combination V5, D3, and J6 to produce its heavy chain, whereas another B cell might use V19, D27, and J6; each combination would result in a unique

16.9 Lymphocyte Development 413

antibody specificity. Similar rearrangements occur in the genes that encode the light chain of the antibody molecule.

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