Mutated VH genes and preferential VH3-21 use define new subsets of XXXX .

@entity1 @entity5 @entity1073
@entity1073 ( @entity1073 ) is believed to originate from a naive B cell. However, we recently demonstrated that a subset of @entity1073 displayed mutated V(H) genes. We also reported restricted use of certain V(H) genes. To assess the prognostic impact of these new findings, we performed V(H) gene analysis of 110 @entity1 , revealing that 18 (16%) @entity1 had mutated and 92 (84%) @entity1 had unmutated V(H) genes. Because the mutation rate was low in the mutated group (2.2%-6.7%), further investigation of the germline V(H) gene in T cells from 5 @entity1 with mutated V(H) genes was carried out; results showed that the unrearranged V(H) gene was identical to the published sequence. These data confirm that the base pair substitutions within the rearranged V(H) genes represent hypermutations, and indicate germinal center exposure. However, V(H) gene mutation status did not correlate with prognosis because there was no difference in clinical outcome between the unmutated and mutated groups. The most frequently used V(H) genes were V(H)3-21 (21 @entity1 ) and V(H)4-34 (19 @entity1 ). A novel finding was that V(H)3-21(+) @entity1073 almost exclusively expressed lambda light chains and displayed highly restricted use of the V(lambda)3-19 gene. V(H)3-21(+) @entity1 had longer median survival than the remaining @entity1 (53 vs 34 months; P =.03), but they tended to be younger at diagnosis. The combined use of V(H)3-21/V(lambda)3-19 suggests a possible role for antigen(s) in the pathogenesis of these @entity5 and indicates that V(H)3-21(+) @entity1 constitute a new @entity1073 entity.
