Differential Usage of an Autoantibody-associated V_H Gene, V_H4-21, by Human B-cell Tumors

Abstract

Selection of immunoglobulin variable region genes for recombination in B cells takes place from among those V_H and V_L gene segments available in the unrearranged germ line repertoire. In the case of neoplastic B cells, there is apparent deviation in the use of V-genes from that expected on a random basis, both for V_H and for V_L. Also, the preferred V-genes, and their patterns of mutation, differ among the various categories of B-cell tumor possibly reflecting the distinct origins and clonal histories on the individual tumor cells. This review focuses on a single V_H gene, V_H4-21, which is a member of the V_H4 family, and which appears selectively to encode immunoglobulins with autoantibody activity, particularly anti-red cell antibodies. The pattern of usage of this V_H gene by B-cell tumors demonstrates clear asymmetry among different tumor types. Also, the mutations detected in this relatively non-polymorphic gene indicate that antigen, possibly autoantigen, may influence the behavior of the tumor cell.

Key Words:

• V_H genes
• V_L genes
• B-cell lymphoma
• autoantibodies
• cold agglutinins
• chronic lymphocytic leukemia