Early studies of animals bearing natural deficiencies in complement C3 and C4 and mice transiently deficient in C3 suggested that the complement system played a role in humoral immunity. Identification and characterization of the complement receptors CD21 and CD35 and their expression on B lymphocytes provided evidence for a direct role for complement in "linkage of innate and adaptive immunity". More recent studies of mice bearing targeted deficiencies in complement proteins C3, C4 or the receptors CD21/CD35 has confirmed the importance of complement in B cell responses in vivo and extended our understanding to distinct stages in B cell differentiation in which complement participates in humoral immunity. In this review, a role for complement is described in five distinct stages of B cell differentiation.