Yonas Bekele1, Mahlet Lemma2, Kidist Bobosha3, Desalegn Yibeltal3, Aikaterini Nasi4, Meseret Gebre5, Anna Nilsson6, Abraham Aseffa3, Rawleigh Howe3, Francesca Chiodi7. 1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Armauer Hansen Research Institute, P.O. Box 1005, Addis Ababa, Ethiopia. Electronic address: yonas.bekele.feyissa@ki.se. 2. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Armauer Hansen Research Institute, P.O. Box 1005, Addis Ababa, Ethiopia; Addis Ababa University, College of Natural Sciences, Ethiopia. 3. Armauer Hansen Research Institute, P.O. Box 1005, Addis Ababa, Ethiopia. 4. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. 5. All Africa Leprosy, Tuberculosis and Rehabilitation Training (ALERT) Center Addis Ababa, Ethiopia. 6. Department of Women's and Children Health, Karolinska Institutet, Stockholm, Sweden. 7. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. Electronic address: francesca.chiodi@ki.se.
Abstract
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 naïve 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 naïve and resting memory (RM) B cells in ART treated children was comparable to control subjects. Profound defects in the homing phenotypes of naïve 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.
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 infectedchildren, aviremic (n = 25) or viremic (n = 13). Frequency of naïve 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 naïve and resting memory (RM) B cells in ART treated children was comparable to control subjects. Profound defects in the homing phenotypes of naïve and memory B cells were identified, with lower CXCR4 and CXCR5 expression. Increased CXCL13 levels were observed in infectedchildren, 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 infectedchildren. CONCLUSIONS: Homing defects of B cells to germinal center may underlie impaired vaccine responses during HIV-1 infection.
Authors: Julia Roider; J Zachary Porterfield; Paul Ogongo; Maximilian Muenchhoff; Emily Adland; Andreas Groll; Lynn Morris; Penny L Moore; Thumbi Ndung'u; Henrik Kløverpris; Philip J R Goulder; Alasdair Leslie Journal: Front Immunol Date: 2019-07-02 Impact factor: 7.561
Authors: Annalisa Dalzini; Maria Raffaella Petrara; Giovanni Ballin; Marisa Zanchetta; Carlo Giaquinto; Anita De Rossi Journal: J Immunol Res Date: 2020-05-16 Impact factor: 4.818