Impaired B cells survival upon production of inflammatory cytokines by HIV-1 exposed follicular dendritic cells.
Follicular dendritic cells (FDCs) are important components in the organization of germinal centers in lymphoid tissue where, following antigen presentation, B cells differentiate into memory B cells. The possibility of establishing primary cell lines from FDCs isolated from lymphoid tissue paved the way for characterization of FDC biological properties. We exposed primary FDC cell lines to HIV-1 strains in vitro and studied changes in the chemo-attractive properties of FDCs and release of inflammatory cytokines.



FDC lines expressed several known and putative HIV-1 receptors; viral genome was amplified in HIV-1 exposed FDCs which released low levels of p24 HIV-1 protein in culture supernatants, but were not definitely proven to be productively infected. Exposure of FDCs to HIV-1 strains did not change the expression of markers used to characterize these cells. HIV-1 exposed FDCs, however, changed the expression of chemo-attractants involved in cell recruitment at inflammatory sites and increased the production of several inflammatory cytokines. The inflammatory milieu created upon HIV-1 exposure of FDCs led to impaired B cell survival in vitro and reduced Ig production.



FDC lines exposed to different HIV-1 strains, although not able to support productive HIV-1 replication, show an increased production of inflammatory cytokines. Our in vitro model of interactions between HIV-1 exposed FDC lines and B cells suggest that exposure of FDCs to HIV-1 in vivo can contribute to inflammation within germinal centers and that this pathological event may impair B cell survival and contribute to impaired B cell responses during HIV-1 infection.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177, Stockholm, Sweden.
Farideh
F
Sabri
Unidad de Immunologia, Instituto de Biopatologia y Medicina Regenerativa, Complejo Hospitalario Universitario de Granada, Granada, Spain.
Alejandro
A
Prados
Unidad de Immunologia, Instituto de Biopatologia y Medicina Regenerativa, Complejo Hospitalario Universitario de Granada, Granada, Spain.
Raquel
R
Muñoz-Fernández
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177, Stockholm, Sweden.
Rebecka
R
Lantto
Unidad de Immunologia, Instituto de Biopatologia y Medicina Regenerativa, Complejo Hospitalario Universitario de Granada, Granada, Spain.
Pablo
P
Fernandez-Rubio
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177, Stockholm, Sweden.
Aikaterini
A
Nasi
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177, Stockholm, Sweden.
Sylvie
S
Amu
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177, Stockholm, Sweden.|Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
Jan
J
Albert
Unidad de Immunologia, Instituto de Biopatologia y Medicina Regenerativa, Complejo Hospitalario Universitario de Granada, Granada, Spain.
Enrique Garcia
EG
Olivares
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177, Stockholm, Sweden. francesca.chiodi@ki.se.
Francesca
F
Chiodi
D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002450:Cell Communication; D002470:Cell Survival; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000821:virology*; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D014779:Virus Replication
D018925:Chemokines; D003470:Culture Media; D016207:Cytokines; D016655:HIV Core Protein p24
B cells; Chemokines; Follicular dendritic cells; HIV-1; Inflammation