This workshop identified several critical gaps in the current understanding of B cell regulatory pathways that impede a more rational development of an effective antibody-based HIV-1 vaccine. For example, broadly neutralizing antibodies in patient serum bind epitopes that are present on monomeric gp120 [25] , yet this is a poor immunogen for neutralizing antibody induction in vaccine recipients. Moreover, as mentioned above, viral epitopes for the known broadly neutralizing MAbs appear to be poorly immunogenic in infected individuals and as vaccine candidates. Insights into the immunoregulation of some of these latter epitopes (e.g., epitopes defined by MAbs 2F5 and 4E10) was provided by recent studies in which the MAbs were discovered to bind one or more self antigens [50, 51] , raising the possibility that these antibody specificities are subjected to negative regulation mechanisms, such as receptor editing or deletion. Thus, Env as an immunogen may bypass key steps in the B cell inductive pathway, or may actively induce negative production or downregulation of production of some broadly neutralizing antibodies [52] [53] [54] .