Numerous studies in several species have shown that certain subsets of T and B lymphocytes express antigen receptors which are either semi-invariant, or germline encoded, and often autoreactive. In the case of B cells they appear to use a distinct immune recognition strategy during developmental selection and functional activation. These B cells respond to foreign antigens, and have the ability to protect against a variety of infections; however, they can also react with self or neoself antigens. They appear to use the latter as positively selecting ligands facilitating their entry into and maintenance in a functional repertoire, as well as providing cues for positioning themselves in strategic microenvironmental niches in the immune system and at interfaces with the environment. These innate-like B cell subsets form a bridge between the rapidly occurring innate immune responses, and the slower acting primary, T cell-dependent, adaptive antibody response by providing a rapid T cell-independent antibody response.