To segregate the many contributions that B cell receptor (BCR)-mediated signals make to immune responses, we have analyzed here B cells deficient in the 'pan-leukocyte' marker CD45. BCR ligation of Cd45-I- B cells failed to activate phosphatidylinositol-3-OH kinase, NF-κB, Erk1 or Erk2 kinases or to upregulate cell survival proteins and instead induced apoptosis. Immunization of Cd45-I- B cell chimeras induced germinal centers and antigen-specific immunoglobulin G1 antibody-forming cells early, but both cellular compartments decreased by day 14. Proliferation of Cd45-I- B cells induced by CD40 ligand in vitro was impaired as a result of abrogation by BCR ligation of the upregulation of prosurvival proteins. In contrast, enforced expression of the antiapoptotic factor Bcl-xL prevented the collapse of Cd45-I- B cell germinal centers. These results show mechanistic differences in B cell survival during germinal center initiation and propagation; CD40 signaling is sufficient for the former, whereas the latter requires signaling from the BCR.