Homing defects of B cells in HIV-1 infected children impair vaccination responses

Background: Successful vaccinations rely on antibody responses. Chemokine receptors play an important role in B cell homing to differentiation niches. We assessed CXCR4, CXCR5 and CCR6 expression on B cells during HIV-1 infection and relate it to antibody responses against a HBV vaccine. Methods: Blood was obtained from 54 healthy controls and 38 ART-treated HIV-1 infected children, aviremic (n = 25) or viremic (n = 13). Frequency of naive and memory B cell subsets was studied by immunostaining. Homing capacity of blood B cells to lymphoid and inflamed tissues was evaluated through CXCR4, CXCR5 and CCR6 expression. Plasma CXCL12 and CXCL13 levels and antibody titers to HBV antigen were determined by ELISA. Results: The frequency of naive and resting memory (RM) B cells in ART treated children was comparable to control subjects. Profound defects in the homing phenotypes of naive and memory B cells were identified, with lower CXCR4 and CXCR5 expression. Increased CXCL13 levels were observed in infected children, inversely correlating to CXCR5 expressing B cell subpopulations. Antibody titers to HBV vaccine correlated with frequency of resting and switched memory B cells in HIV-1 infected children. Conclusions: Homing defects of B cells to germinal center may underlie impaired vaccine responses during HIV-1 infection. (C) 2019 The Authors. Published by Elsevier Ltd.