Role of the mechanisms for antibody repertoire diversification in monoclonal light chain deposition disorders: when a friend becomes foe

The adaptive immune system of jawed vertebrates generates a highly diverse repertoire antibodies to meet the antigenic challenges constantly evolving biological ecosystem. Most diversity is generated by two mechanisms: V(D)J gene recombination and somatic hypermutation (SHM). SHM introduces changes in variable domain antibodies, mostly regions that form paratope, yielding with higher antigen binding affinity. However, recognition only possible if antibody folds into stable functional conformation. Therefore, key force determining survival B cell clones undergoing ability mutated heavy light chains efficiently fold assemble antibody. structural context where selection mutations occurs, both benefit from protective mechanisms counteract potentially deleterious impact changes. patients monoclonal gammopathies, proliferating plasma clone may overproduce chain, which then secreted bloodstream. This places chain out provided quaternary structure antibody, increasing risk misfolding aggregation due destabilizing mutations. Light chain-derived (AL) amyloidosis, deposition disease (LCDD), Fanconi syndrome, myeloma (cast) nephropathy are group diseases derived pathologic chains, recognized play role. In this review, we address promote pathological an emphasis on AL amyloidosis. We also analyze contribution (V L ) segments cytotoxicity, organ tropism, fibrils. Finally, most recent advances development computational algorithms predict role cardiotoxicity amyloidogenic discuss perspectives approach faces.