Background:  B-cell defects associated with HIV-induced immune activation include aberrant terminal differentiation, as evidenced by loss of CD21 expression. In an effort to determine whether HIV-induced skewing of B-cell subsets affect their ability to respond to antigenic stimulation, we investigated B-cell responses to influenza vaccination.

Methods:  We recruited 64 HIV chronically infected patients into 4 groups based on HIV plasma viremia and CD4⁺ T-cell count received the 2003 trivalent inactivated influenza vaccine, along with17 HIV-negative individuals. B cells were analyzed phenotypically and functionally at baseline (D0) and at D7, D28, and D54 post-vaccination. Frequencies of influenza-specific antibody secreting cells were measured by ELISpot assay and antibody responses by hemagglutinin-inhibition assay. Memory response to influenza was measured by ELISpot following polyclonal activation of B cells in vitro.

Results:  The percentage of B cells carrying a memory phenotype, as measured by CD27 expression, was markedly lower in HIV-aviremic but not HIV-viremic patients when compared with HIV-negative individuals. However, in HIV-viremic patients, CD27 expression, also a marker for activation, was markedly increased on CD21-low (activated) compared with CD21-high (resting) subsets of B cells, consistent with previous findings that the CD21-low subset represents aberrantly activated B cells in HIV-viremic patients. Peak antibody responses to influenza vaccination, as measured by anti-influenza antibody-secreting cell frequency and hemagglutinin-inhibition titers to 4 hemagglutinin antigens, were decreased to varying degrees in HIV-infected patients compared with HIV-negative individuals. However, and most strikingly, anti-influenza memory B-cell responses were significantly lower in all categories of HIV-infected patients compared with HIV-negative donors and were directly correlated to CD4⁺ T-cell count and inversely correlated to HIV plasma viremia in a subset of patients.

Conclusions:  All categories of chronically HIV-infected patients had reduced levels of resting memory B cells compared with HIV-negative individuals. This defect translated into a reduced anti-influenza B-cell memory response following influenza vaccination and was likely a contributing factor to the lower baseline levels of hemagglutinin-inhibition titers observed in HIV-infected patients when compared to HIV-negative individuals with similar vaccine histories.

Keywords: B cells; memory response; influenza