Dysfunctions in the migratory phenotype and properties of circulating immature transitional B cells during HIV-1 infection.
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.



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.



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.



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.



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.
aDepartment 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.
Sylvie
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Virginie
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Silvia
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Lopalco
Francesca
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Chiodi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D002454:Cell Differentiation; D002465:Cell Movement; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D054448:Precursor Cells, B-Lymphoid / Q000473:pathology*; D013194:Staining and Labeling; D055815:Young Adult
D044966:Anti-Retroviral Agents