1933 Unexpected Rearrangement and Expression of the Immunoglobulin l 1 Locus in Scid Mice

In severe combined immunodeficient (scid) mice, V(D)J recombination is severely impaired due to a recessive mutation ( scid ). Thus, we were surprised to find in this study that V l 1–J l 1 rearrangement is routinely detectable in scid fetal liver, adult bone marrow, and spleen in the apparent absence of completed VH–DJH and V k –J k rearrangements. Particularly surprising, we found the level of V l 1–J l 1 rearrangement in scid fetal liver to be comparable to that in fetal liver of wild-type mice. The majority of scid V l 1–J l 1 rearrangements contained abnormal deletions at the VJ junction, consistent with the known effect of scid . However, z 15% of V l 1–J l 1 rearrangements lacked abnormal deletions. Productive l 1 transcripts resulting from in-frame rearrangements were readily detectable in scid adult bone marrow and spleen, consistent with our ability to detect l 1-expressing cells by flow cytometry in the spleens of bcl-2– transgenic scid mice. Strikingly, l 1 transcripts from individual scid mice often showed VJ junctional sequences with the same recurring palindromic (P) additions of three, four, or five nucleotides. To account for these findings, we suggest that (a) nonhomologous end joining of V l 1 and J l 1 coding ends in fetal B lineage cells may not be (severely) impaired by scid ; (b) recurring P additions in scid l 1 transcripts may reflect certain molecular constraints imposed by scid on the resolution of V l 1 and J l 1 hairpin coding ends; and (c), scid lymphocytes with productively rearranged V l 1 and J l 1 elements may differentiate into recombinase-inactive cells and emigrate from bone marrow to spleen.