Eight full length cDNA were isolated from EBV transformed human PBL derived from different normal individuals. Five were derived from antibodies with the characteristics of natural polyreactive antibodies. Three were either monoreactive or bireactive. The most striking feature of the structure of these molecules was their utilization of VH families. Although three used the large VHIII family and one used the large VHI family, the other four used genes derived from two of the recently defined small human VH families VHIV and VHV. Three of the molecules represent VHIV expressed sequences and one is the first example of a VHV gene used in an antibody of defined specificity. The nucleotide sequences of some of the molecules were remarkably similar in their VH gene segments to previously described VH genes. The data suggest that natural autoantibodies may use a restricted portion of the VH repertoire, and, in addition, that some polyreactive antibodies may be germ line encoded. The implication of these findings for the origin and diversity of the human B cell repertoire is discussed.

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