THE GENE LOCI FOR IMMUNOGLOBULIN HEAVY-CHAINS IN PRECURSOR B-CELL LINES FROM A PATIENT WITH SEVERE COMBINED IMMUNODEFICIENCY APPEAR ABLE TOPARTICIPATE IN DNA REARRANGEMENT BUT HAVE A GERM-LINE CONFIGURATION

In a previous study (Immunogenetics 1988. 27: 330) with Epstein-Barr v irus, we established lines of precursor B cells from bone marrow cells of a patient with severe combined immunodeficiency in whom the number s of B cells and T cells were markedly reduced. Although based on thei r surface markers these cell lines appeared to be at an early stage of B cell differentiation, the gene loci for immunoglobulin heavy chains (IgH) retained the germ-line configuration on both chromosomes in alm ost all the transformants. In this study, we found that the enhancer s equence, located between the J(H) and mu genes, was hypomethylated and an abundance of the germ-line Cmu transcript was detected in these ce ll lines by Northern hybridization. These results suggest that the chr omatin structure of the IgH gene locus in these cell lines is accessib le to VDJ recombinase and is able to participate fully in DNA rearrang ement. By contrast, we did not detect transcripts of the RAG-1 and RAG -2 genes, which are required for V(D)J recombination at gene loci for immunoglobulin and T cell receptors. Thus, it seems likely that these cell lines fail to initiate the V(D)J recombination process because of some deficiency in the formation of VDJ recombinase, which includes t he inability to express RAG genes.