Evidence for the genomic organization of human lambda light chain joining (J) region gene segments is presented. A mouse J lambda probe was used in Southern hybridizations to localize joining region sequences in a cosmid clone containing the genomic cluster of six human lambda constant (C) region gene segments. The results of these hybridizations suggest the presence of at least one J gene segment upstream from each constant region gene segment. The DNA sequences indicate that the human J lambda 1, J lambda 2, and J lambda 3 gene segments have consensus nonamer and heptamer sequences, proposed to be involved in V-J joining, are capable of encoding the known amino acid sequences for the respective J peptides, and have a sequence which could give a functional RNA splice site at the end of their coding regions. Our data show that a single functional J is located 1.3 or 1.6 kb upstream of each of the C lambda gene segments known to encode the Mcg, Kern- Oz-, and Kern- Oz+ isotypes. Therefore, the gene organization of this region of the human lambda locus is J1C1-J2C2-J3C3. The DNA sequences of J lambda 1, J lambda 2, and J lambda 3 presented in this paper establish that a single J lambda gene segment precedes each expressed C lambda gene segment, and support a model for the evolution of the human lambda JC clusters where J1C1 and J2C2-J3C3 arose from different ancestral JC units.
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