St ruc ture and Expression in B Lympho id Cells

J chain is a 15 kilodalton protein that links together IgM or IgA monomers to form pentameric IgM or dimeric IgA (reviewed in reference 1).The regulation of J chain expression in B cells has been studied by several laboratories in an effort to understand the developmental program of gene activation in the B lymphocyte. Some results suggest that the program for J chain expression may be different between mouse and man. Studies of mouse cell lines representing different stages of B cell differentiation have suggested that J chain expression is a late step of mature B cells; J chain appeared to be absent at the pre-B stage and in cells representative of unstimulated B cells (expressing surface IgM only), but present in large amounts in plasmacytomas and in mitogen-stimulated splenic lymphocytes (2-5). In contrast to this pattern for mouse lymphocytes, several reports have indicated that human lymphocytes may begin J chain expression at an earlier stage (6), perhaps even before synthesis of Ig (7). To further characterize J chain expression in human lymphocytes and to extend the analysis to the DNA level, we have obtained genomic clones for the humanJ chain gene. The cloned gene has been examined by nucleotide sequence analysis to establish its identity as a functional J chain gene. The resulting sequence has been compared with the previously published human J chain sequence, determined at the amino acid level, and with a murine J chain complementary DNA (cDNA) 1 clone. Because of the presence of nine candidate polyadenylation signals (AATAAA or AATTAAA) downstream of the C-terminal coding block in the human clone, the 3' end of the gene could not be established from the sequence alone; S1 nuclease protection experiments using RNA from the B lymphoid line BALM-4 have allowed identification of the functional polyadenylation site. Hybridization probes from the clone have been used to explore the human genome (by Southern blot experiments) for related sequences. Finally, in initial experiments investigating the developmental program of this gene, a cloned J chain probe bas been used to analyze J chain transcripts in a variety of human lymphoid cells representative of pre-B and B cell stages of differentiation.