Life, death, and antibodies

The search for high-affinity antibodies by B cells leaves a trail of molecular destruction The production of high-affinity antibodies has fascinated immunologists for many decades. A potent arm of the immune response, these antibodies are forged in transient tissue structures called germinal centers (GCs) that appear in lymph nodes a few days after an infection is initiated. Over the ensuing days and weeks, the GC witnesses a cellular pantomime that includes rapid bursts of B lymphocyte proliferation and multicellular migratory cycles that have a unique purpose. These B cells are in the act of mutating, reshaping, testing, and improving their antibody specificities. While their antibody is refined, GC B cells are also undergoing further differentiation to be retasked for new, long-term occupations as circulating memory cells in the blood or bone marrow-resident, long-lived plasma cells that will produce high-affinity, protective antibodies for life. These intense proliferation and selection processes are balanced by an extraordinary rate of programmed cell death (apoptosis), and there is much speculation as to how and why so many B cells are targeted for apoptosis. On page 193 of this issue, Mayer et al. (1) identify the paths leading to B cell apoptosis in the GC reaction.