Plasma cells (PC) are antibody secreting cells (ASC) that play a central role in humoral immunity by producing protective antibodies. However, in many autoimmune diseases and in allergy long-lived PC secreting autoantibodies contribute to immunopathology (1). Long-lived PC reside in specialized survival niches and do not proliferate. They are refractory to therapies that target the activation and/or proliferation of lymphocytes (e.g. cyclophosphamide, immunosupressants, and glucocorticoids) (2). They are also not affected by the depletion of their precursors, the B-lymphocytes, with the monoclonal anti-CD20 antibody as PC do not express CD20 (1). Thus, current therapies do not affect autoantibody production and do not have curative potential. Deletion of autoantibody-secreting PC poses a major challenge and seems to be critical to reach long-term, therapy-free remission. Current strategies to deplete PC, such as anti-thymocyte globulin (ATG) (3), proteasome blockade by bortezomib (4), anti-VLA4/anti-LFA1 antibodies (5), or TACI-Ig, are more or less effective, lack selectivity, and often have unwanted side-effects. A selective depletion of antigen-specific PC would limit side-effects and preserve protective antibody titres.
The present invention addresses the issue of elimination of plasma cells secreting specific antibodies