Abstract Is an HIV vaccine possible? Vaccines are one of the most successful public health interventions over the past century. Nearly all vaccines work by induction of protective antibodies. However, our understanding of the cellular dynamics of immune responses to vaccines, particularly the biology surrounding B cell competition within germinal centers (GC) to complex vaccine antigens is limited. This lack of understanding of fundamental B cell biology has contributed to the inability to develop an effective HIV vaccine. Promisingly, a small population of HIV+ individuals have developed broadly neutralizing antibodies (bnAbs), giving renewed hope that an HIV vaccine is possible. Recent work has found that many HIV negative healthy human donors have VRC01-class bnAb precursor B cells. However, work from these studies revealed that these potential bnAb precursor B cells are found at an unusually rare frequency. This suggested that following immunization these B cells may be outcompeted by more frequent non-neutralizing B cells. To answer immunological questions surrounding this problem, I developed a model system utilizing mice containing human genes for the germline-reverted VRC01 bnAb (VRC01gHL). Through this B cell transfer model, we found that antigen affinity, avidity, and precursor frequency all played interdependent roles in competitive success of rare VRC01gHL B cells in GCs. Critically, we found that rare VRC01gHL B cells with physiological affinities could be primed to successfully compete within GCs. However, these responses were limited to specific “GC” islands suggesting B cell competition to seed individual GCs is critical in addition to competition within the GC. Taken together, these observations suggest that B cell immunodominance in the GC microenvironment (GCME) is a major obstacle to overcome in developing a successful HIV vaccine. However, there are significant knowledge gaps pertaining to the physiological conditions in which B cells compete to