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A new human immunoglobulin VH family preferentially rearranged in immature B-cell tumours

Abstract

The prevalent forms of adult and childhood B-cell neoplasia are chronic lymphocytic (CLL) and acute lymphocytic (ALL) leukaemia, and are typified by a nearly monoclonal accumulation of cells expressing a single heavy (H) and light (L) chain variable (V) region. V gene selection could be random, or quite biased if the disease or the developmental status of the transformed cell somehow influenced DNA rearrangement. We have cloned and sequenced three germ-line VH gene segments that constitute a new human VH family (subgroup V) linked within 160 kilobase pairs of the DH-JH complex. One VH(V) member is rearranged in about 30% of patients with CLL and ALL, but not in IgM-expressing B-cell lines from peripheral blood. In some tumours, we detect a truncated ( VH(V) RNA devoid of constant regions that originates from unrearranged VH(V) genes. In other tumours and in resting splenocytes, we detect large amounts of normally sized VH(V)-associated mRNA, although stimulation by mitogen of splenic B cells results in loss of VH(V)-hybridizing RNA. These features suggest that biased rearrangement of subgroup V may be under developmental selection.

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Humphries, C., Shen, A., Kuziel, W. et al. A new human immunoglobulin VH family preferentially rearranged in immature B-cell tumours. Nature 331, 446–449 (1988). https://doi.org/10.1038/331446a0

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