Normal D-JH rearranged products of the IgH gene in SCID mouse bone marrow.

Abstract

SCID mice are profoundly immunodeficient, resulting from an inability to carry out the V(D)J recombination reaction during both B cell and T cell development. Recently, however, it was revealed that normal rearrangement frequently did occur in the TCR delta and gamma chain loci in the SCID thymus. To evaluate whether the normal rearrangement occurring in SCID is a T-cell-specific phenomenon, we directly cloned using PCR the DQ52-JH2 and DFL16.1-JH2 rearranged segments of the IgH gene from SCID bone marrow. The subsequent analysis revealed that normal V(D)J recombination occurred in a significant number of the analyzed clones. By quantitative Southern hybridization it was shown that the quantity of normal DQ52-JH2 joints existing in the SCID bone marrow is approximately 4-7% that in normal bone marrow. D-JH rearrangement in SCID mice and normal mice differs in the frequency of nucleotide insertion (N insertion). Although most of the normal mouse clones exhibited N insertion in the D-JH rearrangement, in SCID mouse clones N insertion was identified in only a few D-JH rearrangements. Furthermore, in several normal rearranged clones, the recombination occurred at the short homologous sequence. These observations suggest that the V(D)J recombination of IgH normally occurs at the early stage of SCID B cell development, just as TCR gene rearrangement occurs during SCID T cell development. Furthermore, the features of rearranged products isolated from SCID bone marrow cells were remarkably similar to those from leaky SCID mice.