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HIV infection is associated with the aberrant expression of B cell receptors for cytokines that regulate B cell activation and differentiation

HIV infection is associated with the aberrant expression of B cell receptors for cytokines that regulate B cell activation and differentiation

HIV infection causes B cell activation and dysfunction that deplete memory B cells and impair isotype diversification of IgG antibodies. Cytokines are critical for B cell activation (e.g. interleukin (IL)-6, interferon (IFN)-γ, IFN-α) and immunoglobulin isotype diversification (e.g. IL-21). As aberrant expression of cytokine receptors, such as the IL-7 receptor, is a characteristic abnormality of CD4+ T cells in HIV patients, we have examined cytokine receptor expression on B cells to gain further insights into B cell dysfunction.

Methods: Expression of receptors for IL-6, IFN-γ (IFNGR1 and IFNGR2), IFN-α (IFNAR1 and IFNAR2) and IL-21 was examined on B cell subpopulations (naïve, switched memory and marginal-zone-like (MZL)), defined by expression of IgD and CD27, in cryopreserved peripheral blood mononuclear cells from HIV patients who were ART naïve (n=10) or ART-treated (n=10) and non-HIV controls (n=10). results: IFNAR1 was increased on naïve (IgD+, CD27-), switched memory (IgD-, CD27+) and marginal zone-like (IgD+, CD27+) B cells (p<0.008) and did not decline on ART. IFNAR2 was also increased on switched memory B cells (p=0.04) but was lower on MZL B cells (p=0.01), returning to normal on ART. IFNGR1 and IFNGR2 were lower on MZL B cells alone (p=0.02 and p=0.005, respectively) and normalised with ART, whereas IFNGR2 was increased on switched memory B cells. IL-21R was increased on all B cell subpopulations (p<0.03) while IL-6R was increased only on switched memory B cells (p=0.04).

Conclusions: B cells of HIV patients exhibit aberrant expression of IFN-α receptors to a greater extent than the IL-6R, suggesting that IFN-α may be more significant than IL-6 in B cell activation. Impaired isotype diversification of IgG antibodies is not associated with decreased IL-21R expression on B cells. Aberrant expression of some receptors persists on ART and might be used as a marker of ongoing B cell dysfunction.

Conference: ASHM 2013

Australian Society for HIV 2013

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