Mouse immunoglobulin gene rearrangements. The sequence of a nonexpressed lambda 3-chain gene

A functionally defective lambda 3-immunoglobulin chain gene has been cloned from plasmacytoma HOPC-1 (gamma 2b, lambda 1). The lambda 3 gene resulted from the juxtaposition of the germline V lambda 1 sequence with a J lambda 3 C lambda 3 gene segment. DNA sequencing of the rearranged V lambda 1 J lambda 3 exon showed the presence of a single base pair deletion at the site of V-J joining. The alteration in the reading frame caused by this deletion generated a stop codon at the 3' end of J lambda 3, thus rendering this gene nonfunctional for light chain production. In addition, a one-point mutation in the J lambda 3-C lambda 3 intron distinguishes the rearranged gene from the unrearranged counterpart. The implications that this rearrangement has in terms of the mechanism of somatic mutations and of selective proliferation of B cells mediated by antigen stimulation are discussed.