The present invention relates to peptide antagonists that bind with high specificity and affinity to B-Lymphocyte stimulator (“BAFF”), thereby antagonizing BAFF receptor (“BAFF-R”) signaling. The invention more specifically relates to VNAR single chain antibodies derived from nurse shark that bind to BAFF, BAFF antagonist compounds and compositions comprising a BAFF specific VNAR binding moiety, methods for preparing them, diagnostic and therapeutic methods of use relating to in vitro or in vivo B cell depletion, e.g., to treat and/or prevent a pathological condition, disorder or disease in which it is beneficial to kill or deplete B cells, such as in autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) or multiple sclerosis (MS), and in certain hematological cancers, including lymphomas, leukemias and myelomas.