The differentiation of B cells along the pathway of B cell development has been well characterized. In the bone marrow, the differentiation from pro-B cells to immature B cells can be defined by several surface antigens, such as a surrogate light chain. Immature B cells become mature B cells and then circulate in the peripheral blood as naive B cells. In the peripheral lymphoid tissues, naive B cells differentiate into memory B cells, which express the CD27 molecule, or plasma cells. Primary immunodeficiencies with hypogammaglobulinemia are caused by defects of the specific molecules which are needed for the B cell differentiation. Recent studies of the genes responsible for such immunodeficiencies have clarified B cell development as well as their pathogenesis. We discuss here the molecules affecting the B cell development and primary immunodeficiencies with hypogammaglobulinemia.