Antibody genes typically undergo several rounds of revision. The gene segments first reshuffle to produce uniquely shaped antibodies. Some B cell genes undergo a further tweak, known as receptor editing, to revamp antibody genes that might lead to attacks on self antigens. The timing of receptor editing is controversial. Most researchers assume it occurs while B cells are maturing in the bone marrow. However, some findings suggest that B cells continue the process even after they relocate to the lymph nodes and spleen.
Wang et al. chanced across fresh evidence while studying the origin of a lymphatic cancer. Whenever it happens, receptor editing involves breaking the DNA and then healing it through a process called non-homologous end-joining (NHEJ). Failure of NHEJ in other situations can lead to cancer-causing chromosome instability, so the researchers wanted to test whether disrupting this type of repair promotes lymphatic tumors.
They created a mouse line in which a key NHEJ gene malfunctions in B cells that have exited the bone marrow. Sure enough, B cell–derived tumors sprouted in the mice. To the researchers' surprise, the cells that gave rise to the tumors had performed not only the initial reshuffling, but also receptor editing, thus supporting the hypothesis that at least some receptor editing occurs outside the bone marrow. The caveat, the scientists say, is that the tumor cells might not duplicate what happens in normal B cells. The benefits of late revisions aren't clear, but they might allow the immune system to further expand its repertoire of antibodies.