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B-lymphocyte dysfunction in chronic HIV-1 infection does not prevent cross-clade neutralization breadth.

ABSTRACT: Aberrant expression of regulatory receptors programmed death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) is linked with dysregulation and exhaustion of T lymphocytes during chronic human immunodeficiency virus type 1 (HIV-1) infection; however, less is known about whether a similar process impacts B-lymphocyte function during HIV-1 infection. We reasoned that disruption of the peripheral B cell compartment might be associated with decreased neutralizing antibody activity. Expression of markers that indicate dysregulation (BTLA and PD-1), immune activation (CD95), and proliferation (Ki-67) was evaluated in B cells from HIV-1-infected viremic and aviremic subjects and healthy subjects, in conjunction with immunoglobulin production and CD4 T cell count. Viral load and cross-clade neutralizing activity in plasma from viremic subjects were also assessed. Dysregulation of B lymphocytes was indicated by a marked disruption of peripheral B cell subsets, increased levels of PD-1 expression, and decreased levels of BTLA expression in viremic subjects compared to aviremic subjects and healthy controls. PD-1 and BTLA were correlated in a divergent fashion with immune activation, CD4 T cell count, and the total plasma IgG level, a functional correlate of B cell dysfunction. Within viremic subjects, the total IgG level correlated directly with cross-clade neutralizing activity in plasma. The findings demonstrate that even in chronically infected subjects in which B lymphocytes display multiple indications of dysfunction, antibodies that mediate cross-clade neutralization breadth continue to circulate in plasma.

SUBMITTER: Boliar S

PROVIDER: S-EPMC3421653 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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B-lymphocyte dysfunction in chronic HIV-1 infection does not prevent cross-clade neutralization breadth.

Boliar Saikat S Murphy Megan K MK Tran T Cameron TC Carnathan Diane G DG Armstrong Wendy S WS Silvestri Guido G Derdeyn Cynthia A CA

Journal of virology 20120523 15

Aberrant expression of regulatory receptors programmed death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) is linked with dysregulation and exhaustion of T lymphocytes during chronic human immunodeficiency virus type 1 (HIV-1) infection; however, less is known about whether a similar process impacts B-lymphocyte function during HIV-1 infection. We reasoned that disruption of the peripheral B cell compartment might be associated with decreased neutralizing antibody activity. Expression of ma ...[more]

PMID: 22623771

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B-lymphocyte dysfunction in chronic HIV-1 infection does not prevent cross-clade neutralization breadth.

Publications

B-lymphocyte dysfunction in chronic HIV-1 infection does not prevent cross-clade neutralization breadth.

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