| Popis: |
The study of immunoglobulin genes in multiple myeloma over the last decade has provided important information regarding biology, ontogenetic assignment, disease evolution, pathogenic consequences and tumor-specific therapeutic intervention. Detailed analysis of V-H genes has revealed the clonal relationship between switch variants expressed by the bone marrow plasma cell and myeloma progenitors in the marrow and peripheral blood. Regarding V-H usage, a bias was found against the V4-34 gene encoding antibodies with cold agglutinin specificity (anti-I/i), thus explaining in part the absence of autoimmune phenomena in myeloma compared to other B cell lymphoproliferative disorders. However, in some studies a substantial number of cases analyzed were carrying the rearranged Hum kappa v325 V kappa gene, known to be over utilized by B cell chronic lymphocytic leukemia clones and possessing autoantibody binding activity. V-H genes accumulate somatic hypermutations following a distribution compatible with antigen selection, but with no intraclonal heterogeneity. The analysis of V kappa genes indicates a bias in usage of V kappa I family members; somatic hypermutation, in line with antigen selection, of the expressed V kappa genes is higher than any other B cell lymphoid disorder. Similar conclusions were reached far V lambda genes; in this case, the analysis raises the controversial issue of N nucleotide insertion at V lambda-J lambda junctions, apparently as a result of TdT activity. A complementary imprint of antigen selection as evidenced by somatic hypermutation of either the V-H or V-L clonogenic genes has been observed. The absence of ongoing somatic mutations in either V-H or V-L genes gives rise to the notion that the cell of origin in myeloma is a post-germinal center memory B cell. |
