Innate-Like B Cells and Their Rules of Engagement

Antibodies are an integral part of the immune system. They are produced in response to an infection or insult but are also present prior to any encounter with antigen as so-called natural antibodies. This review focuses on the tissues and cellular origins of natural antibodies. It summarizes recent data showing that B-1 cells, an innate-like B cell population distinct in development, repertoire, and tissue location from the majority conventional or B-2 cells, are the main contributors of natural antibodies in mice in steady state. Furthermore, they show that natural IgM production appears largely confined to B-1 cell populations in the spleen and bone marrow. In contrast, B-1 cells in the body cavities, sites of predominance of this population, harbor B-1 cells that do not constitutively produce antibodies. Instead, these cells act as rapid immune responders that relocate to secondary lymphoid tissues and differentiate to cytokine and antibody-secreting cells shortly after an infection. Thus, the process of B-1 cell response participation is distinct from that of B-2 cell activation as the accumulation of effector B-1 cells does not rely on extensive clonal expansion, but instead on their rapid migration and redistribution, a process that appears under the control of infection-induced innate signals.