"Amyloid" fibrils have been created from some human Bence Jones proteins by proteolytic digestion under physiologic conditions. These fibrils with an antiparallel, beta-pleated sheet conformation consist of only a portion of the variable region of the immunoglobulin light polypeptide chain and share the physical properties of amyloid fibrils. The relation between amyloidosis and immunoglobulins is thus more firmly established and a pathogenetic mechanism for amyloid fibril formation is suggested.

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synopsisThe presence of the antiparallel-&pleated sheet conformation in isolated human amyloid protein fibrils has been confirmed by infrared spectroscopy. In most amyloid samples, this conformation was enhanced by acidic solution conditions. Infrared spectroscopy (Amide I and Amide V absorption bands) and x-ray diffraction methods were also used to examine the immunoglobulin molecule for solid state @-structure. It was found that both heavy chains and Bence Jones proteins exhibited some @-pleated sheet content upon acid and/or heat treatment. Furthermore, pepsin digests comprising either the variablerich region (Fd') of the immunoglobulin heavy chain or, in particular, filamentous variable segments of x and A Bence Jones proteins were, as isolated, very similar to amyloid in @-structure content. Data from other immunoglobulinderived samples did not exhibit extensive @-pleated sheet content. On the other hand, most smyloid and immunoglobulinderived samples did display some @-structure when cast from 50% HCOOH solution. Under these conditions, however, filamentous light chainvariable segments exhibited welldefined infrared patterns rich in antiparallel+-pleated sheet structure and gave a "cross-@" x-ray diffraction pattern.