IMMUNOGLOBULIN-CHI LIGHT CHAIN GERM-LINE TRANSCRIPTS IN HUMAN PRECURSOR LYMPHOCYTES-B

B lymphoblastoid cell lines (BLCL), established from bone marrow and peripheral blood mononuclear cells from two severe combined immunodeficiency (SCID) patients, manifested a complete absence of genomic rearrangements of the immunoglobulin (Ig) heavy (H) and light (L) chain loci. The BLCL contained germ-line transcripts of the Ig kappa region locus of approximately 1.2 kilobases (kb). By cDNA cloning and sequence analysis the transcripts were shown to consist of a C(kappa) segment, a J(kappa)1 gene segment, 160 base pairs (bp) of J(kappa)1 5' intervening sequence, containing the heptamer/nonamer recombination recognition sequences and at the 5' end a 523-bp segment designated human kappa-degrees, The first 206 bp of this 5' segment were homologous to the reported murine kappa-degrees region. Genomic restriction mapping and DNA sequence analysis demonstrated that the human kappa-degrees segment is located approximately 4 kb upstream of J.1. The kappa-degrees segment contains a putative promoter region with an OCT2 binding site, and has a splice donor site to accomplish splicing to an acceptor site 160 bp upstream of J(kappa)1. Expression of the kappa-degrees gene segment was found in BLCL derived from normal fetal bone marrow, in which both Ig kappa loci were in the germ-line configuration. These findings indicate that the described transcripts are not only present in SCID, but also in normal developing pre-B lymphocytes. The expression of germ-line Ig kappa L chain transcripts may be associated with the locus becoming accessible to gene rearrangement.