Antiviral antibody responses in infants are limited in quality. One reason for this finding could be that the majority of B cells in infants are CD5 super(+) cells, a subset of B cells that is thought to contain cells expressing polyreactive, low-affinity B cell receptors. We analyzed the rotavirus (RV)- specific antibody heavy chain variable region (VH) repertoire in CD5 super(+) and CD5 super(-) B cells of four RV-infected children between 10 and 19 months of age. We found that the RV-specific B cell repertoire in CD5 super(+) cells was VH3 family biased, in contrast to the VH1/VH4 dominance seen in CD5 super(-) B cells. The immunodominant RV-specific gene segment in CD5 super(-) B cells was VH1-46, which is the dominant segment used in RV-specific peripheral blood B cells from infants and adults. In contrast, the immunodominant gene segment was VH3-23 in RV- specific CD5 super(+) B cells, which is the dominant gene segment in randomly selected B cells. Both RV-specific CD5 super(+) and RV-specific CD5 super(-) B cells from all children studied demonstrated very low frequencies of somatic mutations. In conclusion, CD5 super(+) B cells in infants responding to RV use an antibody gene repertoire that differs from the virus-specific repertoire of CD5 super(-) B cells, and both CD5 super(+) and CD5 super(-) RV-specific B cells exhibit a low frequency of somatic mutations.