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The gene loci for immunoglobulin heavy chains in precursor B cell lines from a patient with severe combined immunodeficiency appear able to participate in DNA rearrangement but have a germ‐line configuration

In a previous study (Immunogenetics 1988. 27: 330) with Epstein‐Barr virus, we established lines of precursor B cells from bone marrow cells of a patient with severe combined immunodeficiency in whom the numbers of B cells and T cells were markedly reduced. Although based on their 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 almost all the transformants. In this study, we found that the enhancer sequence, located between the Jh and μ genes, was hypomethylated and an abundance of the germ‐line Cμ transcript was detected in these cell lines by Northern hybridization. These results suggest that the chromatin structure of the IgH gene locus in these cell lines is accessible to VDJ recombinase and is able to participate fully in DNA rearrangement. 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 the inability to express RAG genes.