V-H gene usage in multiple myeloma: Complete absence of the V(H)4.21 (V(H)4-34) gene

The immunoglobulin heavy chain variable region (V-H) gene usage in multiple myeloma (MM) has not been reported, although a few studies have incidentally identified the V-H gene rearranged in small cohorts of MM patients. We used a reverse trancriptase-polymerase chain reaction based technique to analyze the V-H gene usage in MM. The V-H sequences were obtained after amplification of bone marrow cDNA using the seven V-H family-specific and constant region primers. The V-H sequences of 72 patients were successfully identified. The frequency of V-H family usage in decreasing order was V(H)3 >V(H)4 >V(H)1 >V(H)5 >V(H)2 >V(H)6 >V(H)7 and corresponded to the functional germline complexity of the V-H families. Individual V-H genes (V(H)1-69, V(H)3-9, V(H)3-23, and V(H)3-30) were overrepresented in our cohort of MM patients; some V-H genes [V(H)3-49, V(H)3-53, and V(H)4.21 (V(H)4-34)], which are rearranged with increased frequency in normal circulating B cells, autoimmune diseases, and other B-cell malignancies, were not detected in any MM patient. Compared with germline sequences, an average of 8.8% (range, 2.7% to 16.5%) of the nucleotides had evidence of mutation within each VH sequence. Based on these results, we conclude that (1) the V-H gene usage in MM is unique compared with other malignant and nonmalignant B-cell populations, (2) the physiologic process of clonal deletion functions to remove clones that have rearranged V-H genes (V(H)4.21) capable of expressing antibodies, which recognize self-antigens, and (3) the complete lack of V(H)4.21 gene rearrangement may help to partially explain the paucity of autoimmune phenomena in MM. (C) 1996 by The American Society of Hematology.