Double TIP-ping

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Science  20 Aug 2010:
Vol. 329, Issue 5994, pp. 914-915
DOI: 10.1126/science.1194316

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B cells of the mammalian immune system use two different means of shuffling gene segments to generate antibodies that recognize pathogens. Unique variable regions of the heavy- and light-chain subunits that constitute an antibody are genetically encrypted through DNA recombination during B cell development (1). The process generates millions of naïve B cell clones, each expressing a distinct antibody whose variable portion recognizes a particular antigen of a pathogen. Upon recognizing a specific antigen, a naïve B cell differentiates into an antibody-secreting plasma cell by further shuffling gene segments that encode the constant region of the heavy chain, while holding the variable region fixed (2). This process, called class switch recombination, is initiated by the enzyme activation-induced cytidine deaminase (AID) (3). On page 917 of this issue, Daniel et al. (4) identify a dual actor in the molecular steps that precede and follow AID action, thereby enabling class switch recombination and refinement of the antibody repertoire.