Role of light chain variable region in myeloma with light chain deposition disease: Evidence from an experimental model

Abstract

Light chain deposition disease (LCDD) results from a propensity of some human monoclonal L chains to form tissue deposits. We designed an experimental model for in vivo expression of human κ L chain sequences in mice and compared a somatically mutated LCDD chain with a closely related control κ chain, both encoded by the unique VκIV gene. Mice secreting the LCDD chain but not those producing the control chain showed deposits with a distribution similar to that observed in patients. These data show that discrete changes in V region sequences can play a major role in tissue deposition of human L chains.