Frequency of VH-gene utilization in human EBV-transformed B-cell lines: the most JH-proximal VH segment encodes autoantibodies.

We have studied VH-gene utilization in a collection of 187 IgM-secreting EBV-transformed cell lines and have begun to correlate VH-gene family expression with binding properties of the secreted immunoglobulins. The results of these studies demonstrate that (1) frequency of VH-gene utilization in fetal and adult tissue-derived cell lines correlates with the complexity of the family and (2) the single-membered most JH-proximal VH-6 family encodes autoantibodies reminiscent of autoantibodies found in the sera of patients with systemic lupus erythematosus. Nucleotide sequence analysis of VH-6-expressing clones revealed that each clone utilizes a short DH segment, resulting in a CDR3 region of conserved length. Our data suggest that EBV does not selectively transform human B cells on the basis of VH-gene family expression and that the VH-6 family encodes polyspecific autoantibodies that may serve an important regulatory function in the immune system.