Human herpesvirus-8 infection leads to expansion of the preimmune/natural effector B cell compartment.
BACKGROUND
Human herpesvirus-8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS) and of some lymphoproliferative disorders of B cells. Most malignancies develop after long-lasting viral dormancy, and a preventing role for both humoral and cellular immune control is suggested by the high frequency of these pathologies in immunosuppressed patients. B cells, macrophages and dendritic cells of peripheral lymphoid organs and blood represent the major reservoir of HHV-8. Due to the dual role of B cells in HHV-8 infection, both as virus reservoir and as agents of humoral immune control, we analyzed the subset distribution and the functional state of peripheral blood B cells in HHV-8-infected individuals with and without cKS.


RESULTS
Circulating B cells and their subsets were analyzed by 6-color flow cytometry in the following groups: 1- patients HHV-8 positive with classic KS (cKS) (n = 47); 2- subjects HHV-8 positive and cKS negative (HSP) (n = 10); 3- healthy controls, HHV-8 negative and cKS negative (HC) (n = 43). The number of B cells belonging to the preimmune/natural effector compartment, including transitional, pre-naïve, naïve and MZ-like subsets, was significantly higher among HHV-8 positive subjects, with or without cKS, while was comparable to healthy controls in the antigen-experienced T-cell dependent compartment. The increased number of preimmune/natural effector B cells was associated with increased resistance to spontaneous apoptosis, while it did not correlate with HHV-8 viral load.


CONCLUSIONS
Our results indicate that long-lasting HHV-8 infection promotes an imbalance in peripheral B cell subsets, perturbing the equilibrium between earlier and later steps of maturation and activation processes. This observation may broaden our understanding of the complex interplay between viral and immune factors leading HHV-8-infected individuals to develop HHV-8-associated malignancies.
Department of Biomedical Sciences and Technologies, University of Milan, Milan, Italy. silvia.dellabella@unimi.it
Silvia
S
Della Bella
Adriano
A
Taddeo
Elena
E
Colombo
Lucia
L
Brambilla
Monica
M
Bellinvia
Fabrizio
F
Pregliasco
Monica
M
Cappelletti
Maria Luisa
ML
Calabrò
Maria Luisa
ML
Villa
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D019288:Herpesvirus 8, Human / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D012514:Sarcoma, Kaposi / Q000097:blood / Q000276:immunology* / Q000821:virology; D019562:Viral Load / Q000276:immunology