Secondary V(D)J recombination in B-1 cells

B-1 B cells are a self-renewing population of B cells that differ from conventional B cells (B-2 cells) in that they are particularly predisposed to auto-antibody production(1-3). Although much is known about the signalling pathways that control B-1-cell growth and development (reviewed in ref. 4), less is known about why these cells are prone to produce autoreactive antibodies. Here we show that B-1 cells, like germinal-centre B cells(5-8), can express recombinase-activating genes 1 and 2 (RAG1 and RAG2) and undergo secondary V(D)J recombination of immunoglobulin genes. In addition, B cells from autoimmune-prone NZB mice show high levels of RAG messenger RNA and recombination. We propose that secondary immunoglobulin-gene rearrangements outside organized lymphoid organs may contribute to the development of autoreactive antibodies.