Clinical Mass Spectrometry Approaches to Myeloma and Amyloidosis

Key points

Background

Plasma cells are terminally differentiated B cells that produce large quantities of immunoglobulin (also called antibody; Fig. 1 ), which serves as the body’s defense against foreign invaders. A plasma cell clone is defined by the unique immunoglobulin produced by that clone. The uniqueness of the immunoglobulin stems from the complementary determining region (CDR), which is an aptly suited N-terminal sequence for binding with a foreign protein. Before maturing into a plasma cell, B cells undergo somatic rearrangement of both the heavy chain and light chain (LC) immunoglobulin genes, resulting in a variation in sequence from the germ line. Once the B cell encounters a foreign antigen, a process of maturation ensues with the end result of a plasma cell clone. Determining the repertoire of plasma cell clones within a particular individual could provide insight into the diversity of antigen exposure. Because plasma cells mostly reside in bone marrow, attempting to determine the CDR sequence diversity by DNA sequencing is very difficult because plasma cell sampling is, at best, incomplete. ¹ Plasma cells self-amplify their CDR region by producing large amounts of immunoglobulins, which result in total serum immunoglobulin levels of 10 g/L. The unique sequence along with their high abundance in serum make immunoglobulins and plasma cell disorders (PCDs) an attractive target for current proteomics techniques.