In the adult mouse, three major subsets of mature B-lymphocytes are recognized: B-1, marginal zone (MZ), and follicular (FO) B cells. These B lymphocytes are the products of B-cell precursors that follow developmental programs that require passage through successive checkpoints to produce appropriately matured B-cell clonotypes. Comparative studies of human subjects found patterns of development and subset composition that are similar, but not identical, to those observed in mice. This chapter focuses on the derivation, development, compartmentalization, and function of these three major B-cell subsets: B-1, MZ and FO. Discussion of the developmental fate of these cells after exposure to antigen, including germinal center formation, class switching, memory B cell, and plasma cell development, can be found in other chapters of this textbook.