The variable regions of immunoglobulin heavy chains are encoded in the germ line by three discrete DNA segments: VH (variable) elements, D (diversity) elements and JH (joining) elements. During the differentiation of B lymphocytes, individual segments from each group are brought together by recombination to form the complete VHDJ H variable region1-8. To understand these processes better, we have now isolated and sequenced molecular clones representing intermediates (DJH fusions) and final products ( V H-to-DJH joins) of heavy-chain gene rearrangement in two cell lines9,10 that represent analogues of cells at early stages of B-lymphocyte differentiation11-13. Heavy-chain gene assembly in one cell line but not in the other is accompanied by the appearance of short nucleotide insertions at the recombinational junctions. The generation of such insertions is positively correlated with the expression of terminal deoxynucleotidyl transferase in these lines.
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