Bw. Baker et al., DISTINCTIVE FEATURES OF IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION GENE REARRANGEMENT IN MULTIPLE-MYELOMA, Leukemia & lymphoma, 14(3-4), 1994, pp. 291-301
We have analysed the rearranged Ig heavy chain (IgH) genes in a series
of 28 cases of multiple myeloma (MM), in order to extend the study of
Ig heavy chain variable (V-H) gene usage in B lymphoid malignancies a
nd to explore the ontogenic compartment from which transformed precurs
or cells arise in this disease. We were able to amplify 28 rearranged
alleles by polymerase chain reaction from 23 of these cases, using a c
ommon joining region (J(H)) amplimer together with a panel of V-H fami
ly-specific amplimers. The pattern of V-H family usage was similar to
that reported in normal peripheral blood B cells with infrequent usage
of V(H)5 and V(H)6 genes. However, nucleotide sequence analysis of 17
IgH alleles revealed rearrangement of other V-H family members, close
ly related to known developmentally regulated V-H genes, some of which
are known to be associated with autoimmune specificities. In contrast
to previous findings on more immature B lineage malignancies, the rea
rranged genes diverged extensively from consensus germline sequences,
consistent with somatic mutation. These findings support the hypothesi
s that the major proliferating precursor in MM arises at, or following
a stage of T cell-dependent germinal centre proliferation in lymphoid
follicles.