B cell development and pneumococcal immunity in vertically acquired HIV infection

• Main Author: Eisen, S.
• Published: University College London (University of London) 2014
• Subjects: 618.92
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.631832

Globally, the population of vertically HIV-infected young adults is increasing. The effect of vertically acquired HIV infection on B cell development and adaptive immunity is relatively unexplored. HIV infection is known to result in perturbations in B cell turnover and signalling, reflecting an accelerated drive to terminal differentiation. Whilst control of HIV load with ART is generally reported to result in recovery of normal B cell dynamics, persistent damage to memory B cell populations is well described and generation of new memory responses may remain impaired. This thesis explores how the development of B cell memory and the immune response to pneumococcus is altered when ‘immune education’ in early life occurs in the context of vertically acquired HIV infection. Young adults with vertically acquired infection were compared with those infected horizontally in early adulthood and with healthy adults. HIV infection was associated with expanded populations of abnormally activated and immature B cells compared to healthy controls. Vertically infected patients showed decreased marginal zone and switched memory populations compared to the horizontally infected group, especially in those patients with controlled HIV viral load. HIV-infected patients showed impaired baseline anti-pneumococcal immunity and diminished humoral responses to immunisation with the pneumococcal polysaccharide vaccine, with a trend to lower antibody concentrations in the vertically compared to the horizontally infected population. There was some suggestion of benefit of early sustained viral control in the vertically infected group. In those patients infected with HIV from early childhood, damage to B cell memory populations and impairment of generation of humoral immunity to pneumococcus is evident in early adult life. It appears likely that viral control in early childhood may help to limit this damage.