The stimulus induced via the B cell receptor is a major factor in determination of the fate of naive B cells resulting in activation, elimination or anergy. The strength of B cell signal transduction is dependent not only on the affinity of antigen binding, but by positive signals via the co-receptor CD21/CD19/Tapa-1. Absence of CD21 expression by B cells results in an impaired humoral response to T-dependent antigens which is characterized by a reduction in B cell follicular retention and germinal center survival. The ligand for CD21 is complement C3d which becomes attached to antigen on activation of the complement system. Thus, the complement system of innate immunity is an important regulator of B lymphocytes.