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Dysfunctions in the migratory phenotype and properties of circulating immature transitional B cells during HIV-1
Sylvie Amu1, Virginie Fievez, Silvia Nozza
1aDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden bImmunology and Infectious Diseases, GIGA-Signal Transduction, University of Liège, Liege, Belgium cDepartment of Infection and Immunity, HIV Clinical and Translational Research, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg dDepartment of Infectious and Tropical Diseases eDivision of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
Objective:
The frequency of immature transitional B cells is increased in blood of HIV-1-infected individuals. We investigated whether HIV-1 infection affects expression and function of chemokine receptors important for egress of immature transitional B cells from bone marrow and migration to lymphoid organs.
Design:
This is a cross-sectional study analysing the migratory phenotype and function of immature transitional B cells in HIV-1-infected individuals, in relation to antiretroviral treatment and age.
Methods:
Frequency of blood immature transitional B cells and their phenotypic characteristics, including chemokine receptors and a maturation marker, were determined by immunostainings. Migratory capacities were studied in a migration assay.
Results:
The increased frequency of immature transitional B cells in untreated HIV-1 infection was normalized in patients receiving antiretroviral treatment; in our cohorts, age did not have an impact on the frequency of circulating immature transitional B cells. Immature transitional B cells from nontreated patients expressed low levels of CD21 molecule. We found an elevated frequency of CXCR3 and CXCR4 expressing immature transitional B cells in treated and nontreated patients. CXCR4 receptor was unresponsive to CXCL12 ligand in in-vitro migration and internalization assays. In addition, CXCR5 expression was downregulated on immature transitional B cells from infected patients, and these cells migrated poorly in response to CXCR5 ligand.
Conclusion:
Circulating immature transitional B cells from HIV-1-infected patients are not fully mature, probably due to premature egress from bone marrow; these cells showed a phenotype which could impair entry into secondary lymphoid organs. Changes in migratory capacity of immature transitional B cells may affect B-cell maturation during HIV-1 infection.
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