In man and in mouse, B-cell maturation occurs in steps, first in the bone marrow from hematopoietic precursors to immature/transitional B cells, then in the periphery from transitional to fully mature B cells. Each developmental step is tightly controlled by the expression and function of the B-cell receptor (BCR) and by the ability to interact with the microenvironment. Mature B cells collaborate with T cells in the adaptive immune response, leading to the production of high-affinity antibodies. This response is very accurate, but slow. Immediately after pathogen entry, however, antibodies already present in the serum reinforce the innate immune response and contribute to the first-line defense against infection. Low-affinity natural antibodies are produced by B-1a B cells in the mouse and immunoglobulin M (IgM) memory cells in man. These antibodies represent an immediate protection against all microorganisms and the only one against encapsulated bacteria. B-1a and IgM memory B cells may function as a link between the innate and adaptive immune response and thus perform a primordial B-cell function.