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

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Amu S, Fievez V, Nozza S, Lopalco L, Chiodi F,


Amu S, Fievez V, Nozza S, Lopalco L, Chiodi F, (click to view)

Amu S, Fievez V, Nozza S, Lopalco L, Chiodi F,

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AIDS (London, England) 2016 6 8()

Abstract
OBJECTIVE
The frequency of immature transitional (IT) 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 IT B cells from bone marrow and migration to lymphoid organs.

DESIGN
This is a cross-sectional study analysing the migratory phenotype and function of IT B cells in HIV-1 infected individuals, in relation to ART and age.

METHODS
Frequency of blood IT B cells and their phenotypic characteristics, including chemokine receptors and a maturation marker, were determined by immunostainings. Migratory capacities of IT cells were studied in a migration assay.

RESULTS
The increased frequency of IT B cells in untreated HIV-1 infection was normalized in patients receiving ART; in our cohorts, age did not have an impact on the frequency of circulating IT B cells. IT B cells from non-treated patients expressed low levels of CD21 molecule. We found an elevated frequency of CXCR3 and CXCR4 expressing IT B cells in treated and non-treated patients. CXCR4 receptor was unresponsive to CXCL12 ligand in in vitro migration and internalization assays. In addition, CXCR5 expression was down-regulated on IT B cells from infected subjects and these cells migrated poorly in response to CXCR5 ligand.

CONCLUSIONS
Circulating IT B cells from HIV-1 infected subjects are not fully mature, probably due to premature egress from BM; these cells showed a phenotype which could impair entry into secondary lymphoid organs. Changes in migratory capacity of IT B cells may affect B cell maturation during HIV-1 infection.

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