Follicular lymphoma immunoglobulin kappa light chains are affected by the antigen selection process, but to a lesser degree than their partner heavy chains

Follicular lymphoma cells carry surface immunoglobulin whose heavy chain variable (V-H) regions exhibit considerable divergence from the aminoacid sequence predicted by the germline nucleotide sequence as a result of the somatic hypermutation process. The present study examined the extent of somatic hypermutation in follicular lymphoma kappa light chain variable region (V kappa) genes about which the available data is limited. DNA extracted from fresh frozen lymph node tissue of 14 patients with follicular lymphoma at diagnosis was subjected to polymerase chain reaction (PCR) amplification aimed at detecting clonal V-H and V-L (L: light chain) gene rearrangements. Clonal V kappa gene rearrangements were detected in 10/14 cases. Amplified V-H and V kappa genes of these 10 cases were directly sequenced by the dideoxy-chain termination method. In all cases, rearranged V-H genes demonstrated numerous mutations clustering in the complementarity determining regions (CDRs), in keeping with previous reports, The degree of divergence of the rearranged V kappa genes from the closest homologous germline V kappa genes varied significantly. Furthermore, two patterns of mutations were observed: (i) in six cases (60%), mutations were most often of the replacement (R) type (changing the aminoacid sequence of the encoded polypeptide) in the CDRs and of the silent (S) type (leaving the aminoacid sequence of the encoded polypeptide unchanged) in the framework regions (FWRs) resulting in R:S ratios significantly greater than would have occurred by chance; (ii) in four cases (40%), very few or no mutations were observed and the distribution of mutations as well as the R:S mutation ratios did not differ significantly from what would have occurred by chance alone. These findings imply that, compared to their partner heavy chains, the kappa light chains of follicular lymphoma neoplastic B-cells' surface immunoglobulin (sIg): (i) are less affected by somatic hypermutation; (ii) play a less significant role in the antigen selection process.