THE INHIBITORY Fcy-RECEPTOR MB (CD32B) IS HIGHLY EXPRESSED ON CLONAL PLASMA CELLS FROM PATIENTS WITH SYSTEMIC LIGHT-CHAIN (AL) AMYLOIDOSIS AND PROVIDES A TARGET FOR MONOCLONAL ANTIBODY THERAPY

摘要

Systemic light-chain (AL-) amyloidosis is a rare and usually fatal disorder (1,2). The median survival of patients seen within 1 month of diagnosis is about 1 year without treatment. Patients with congestive heart failure survive 4 to 6 months AL- amyloidosis is usually an immunoglobulin light-chain-mediated disease and over 95% of patients have measurable serum free light chains. AL-amyloidosis is a clonal plasma cell dyscrasia, with the majority of patients having less than 20% plasma cells in the marrow The clonal plasma cells are usually indolent and do damage by secreting toxic proteins (3,4) Their cell-surface endowment has not been well studied. They express CD138 and sometimes CD20, although that is controversial, and variably and aberrantly express CD52 (5,6) The Fey receptor system represents a balance of activating and inhibitory cell-surface receptors that modulate immune complex-mediated processes such as inflammation and autoimmunity (7,8) A role for this system in plasma cell dyscrasias has not been identified. The low-affinity IgG Fc-receptor (FCGRIIB or CD32B) is found on B cells and modulates humoral immune function in a number of settings. CD32B knock-out mice possess enhanced antibody responses and could spontaneously make anti-DNA and anti-IgG antibodies in certain susceptible strains; overexpression of CD32B in lupus-prone mouse strains restores tolerance and reduces ANA titers (9, 10) The receptor on B cells, designated as CD32B1, is not internalized, unlike the CD32B2 isoform found on myeloid cells CD32B1 has been shown to be a promising target for cytotoxic humanized anti-CD32B monoclonal antibodies in a murine lymphoma xenograft model In this report, we show that CD32B is highly expressed on the surface of clonal plasma cells from AL-amyloidosis patients, providing a target for monoclonal antibody therapy.