In the hypothesis that pre‐existing, germline‐encoded antibodies (naturally occurring antibodies, NAb) bind to conserved epitopes on invading nonself antigens, bound NAbs may initiate complement deposition and become targets of nascent C3b, which generates C3b–C3b–NAb complexes that remain associated with the nonself antigen (C3b–C3b–NAb…antigen). The inactivated form of these complexes (C3dg–C3dg–NAb…nonself antigen) may bind bivalently and thus firmly to B cells via CR2, a process stimulating antigen presentation. In some cases, CR2‐bound ‘C3dg–C3dg–NAb…antigen complexes’ may further be recognized by immunoglobulin (Ig) determinants on B cells, whereby an immune response is elicited. As conserved epitopes on the nonself antigen are already complexed to NAbs, only B cells carrying Ig determinants specific for nonself epitopes may be stimulated. This hypothesis can explain directed affinity maturation towards nonself, protection from a strong immune response to conserved epitopes, down‐regulation of antibody formation and unresponsiveness to high‐dose antigen.