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

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.