Light chain myeloma plasma cells induce a strong cell-mediated immune response mainly directed against the monoclonal light chain determinants in a murine experimental model.
An important goal for the treatment of human B cell malignancies lies in the induction of an active immune response directed against the tumoral clone, and more particularly against antigenic determinants of the monoclonal immunoglobulin (Ig). The presence of idiotype-reactive T-cells in patients with multiple myeloma has been previously reported, and strategies to increase their responsiveness towards the malignant plasma cells are being actively explored. Light chain (LC) myeloma is often an aggressive form of the disease, regarding which antitumoral immunity has not yet been studied. Here, we investigated in an experimental murine model a secreted monoclonal LC that may behave as a strong tumor antigen after immunization of animals with mitomycin C-treated malignant plasma cells producing monoclonal Ig. Non-dividing plasma cells were utilized as a cell suspension to immunize the mice intraperitoneally (i.p.). The immunized mice produced anti-Ig LC antibodies, mounted a cell-mediated response mainly directed against the monoclonal LC determinants, and survived tumor challenge with significant frequency. These results suggest that plasma cells are capable of presenting antigenic determinants derived from a secreted monoclonal LC in an MHC class I context, and of predominantly inducing a monoclonal Ig-specific T-cell response which can contribute to tumor rejection.
Galea
Horia Radu
HR
Immunology Laboratory, CNRS UMR 6101, University Hospital, 2 rue du Dr. Marcland, 87042 Limoges, France.
Denizot
Yves
Y
Cogné
Michel
M
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D007114:Immunization; D007147:Immunoglobulin Light Chains / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000951:Antigens, Neoplasm; D007147:Immunoglobulin Light Chains