A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens. Display omitted •Engineered germline-targeting HIV proteins are required to activate naive B cells•Native-like HIV proteins do not activate naive B cells•Native-like HIV proteins are needed to select for broad neutralization against HIV•Vaccination against HIV requires immunization with a succession of immunogens Different viral antigens are required to initiate and then to drive the selection of HIV broadly neutralizing antibodies, showing that vaccination to induce HIV protection in humans will likely require immunization with a succession of related immunogens.