Background: An accumulation of late-differentiated CD8+ T-cells together with fewer B-cells and seropositivity for cytomegalovirus (CMV) characterises an ‘immune risk profile' associated with mortality in elderly people and represents one of the hallmarks of ‘immunosenescence'. Objectives: While differences in memory T-cell phenotypes between young and old people have been intensively studied, and the role of CMV is well-accepted as a driving force in this regard, the impact of CMV on B-cells, if any, has been relatively neglected thus far. Methods: Here, we avail ourselves of blood samples from participants of the Berlin Aging Study II (BASE-II) to compare peripheral blood B-cell differentiation phenotypes of 140 age- and gender-matched CMV-seronegative or -seropositive adults aged between 24 and 85 years using multicolour flow cytometry analysis. Results: We found that the frequencies of naïve B-cells within the CD19+ population were not significantly different in younger and older CMV-seronegative people. This was also true in CMV-seropositive subjects. The frequencies of late-differentiated B-cells were also not different in CMV-negative elderly and young. However, in marked contrast to the T-cell compartment, this was also true for late differentiated B-cells. Within age groups, the most marked differences in the distribution of B-cell phenotypes were between CMV-seronegative and -seropositive subjects, for both genders. Conclusion: These results emphasize the importance of including CMV serostatus in the analysis of immune signatures. Because the proportion of the population infected with CMV increases with age, the effect of CMV rather than age could confound analyses seeking age-associated changes to human immunity.