In light of the findings that BAFF is elevated in SLE and greatly elevated following B cell depletion and the recent failure of anti-CD20 antibody, a B cell depleting antibody to demonstrate clinical efficacy in the treatment of SLE despite successful B cell depletion, our data suggest that B cell depletion may only be effective if the re-emergence of high affinity autoreactive B cells can be kept in check. The gene discussed is TNFSF13B; the disease is systemic lupus erythematosus.