Abstract
BackgroundHuman immunodeficiency virus type 1 (HIV-1) induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation.Methods/Principal FindingsWe evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and phenotype of primary B cells in vitro. Moreover, we examined expression of activation-induced cytidine deaminase (AID) mRNA that is responsible for class switch recombination (CSR) and somatic hypermutation (SHM). Here, we report that changes observed in cellular proliferation, phenotypes and activation of B cells could be caused by direct contact between HIV-1 particles and primary B cells in vitro. Finally, direct HIV-1-derived B cells activation led to the increase of AID mRNA expression and its subsequent CSR function was detected in vitro.Conclusion/SignificanceWe showed that HIV-1 could directly induce primary B cells dysregulation triggering phenotypical and functional abilities of B cells in vitro that could explain in some extent early B-cell abnormalities in HIV disease.
Highlights
B cells are a critical component of the adaptive immune system, by producing highly specific antibodies and by establishing a CD27+ memory B cells
After 6 days of treatment B cells survival was better when cells were treated with Human immunodeficiency virus type 1 (HIV-1), with CD40L/interleukine 4 (IL-4) or with LPS/IL-4 where an average of 40–60% of living B cells in comparison with boiled Human Immunodeficiency Virus (HIV)-1 condition or with non-treated cells (Figure 1A) as NT condition at day 1 corresponded to 100% of B-cell survival
We have found that these functional features of human primary B cells in vitro were adversely affected by the direct interaction with HIVNL4-3 particles
Summary
B cells are a critical component of the adaptive immune system, by producing highly specific antibodies and by establishing a CD27+ memory B cells. During HIV infection and in humoral immunity context, initial observations revealed that patients with acquired immune deficiency syndrome (AIDS) could exhibit hyperimmunoglobulinemia, increasing expression of cell-activation markers, depletion of memory B cells inducing ineffective recall responses, polyclonal B-cell hyperactivity, and altered differentiation of naıve B cells that could result in impaired immunoglobulin class switch recombination (CSR), and production of nonspecific immunoglobulin (Ig)G, IgE and IgA antibodies [3,4,5,6,7,8] All of these processes provoke defective responses to opportunistic pathogens and vaccines [7,9]. A direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation
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