Affinity-driven selection of B lymphocytes within germinal centers is critical for the development of high-affinity memory cells and host protection. To investigate the role of the CD21/CD35 coreceptor in B cell competition for follicular retention and survival within the germinal center, either Cr2(+) or Cr2(null) lysozyme-specific transgenic B cells were adoptively transferred into normal mice immunized with duck (DEL) or turkey (TEL) lysozyme, which bind with different affinities. In mice injected with high-affinity turkey lysozyme, Cr2(null) B cells responded by follicular retention; however, they could not survive within germinal centers. This suggests that CD21 provides a signal independent of antigen that is required for survival of B cells in the germinal center.