title: Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals.
abstract: Human immunodeficiency virus (HIV) disease leads to impaired B cell and antibody responses through mechanisms that remain poorly defined. A unique memory B cell subpopulation (CD20(hi)/CD27(lo)/CD21(lo)) in human tonsillar tissues was recently defined by the expression of the inhibitory receptor Fc-receptor-like-4 (FCRL4). In this study, we describe a similar B cell subpopulation in the blood of HIV-viremic individuals. FCRL4 expression was increased on B cells of HIV-viremic compared with HIV-aviremic and HIV-negative individuals. It was enriched on B cells with a tissuelike memory phenotype (CD20(hi)/CD27(-)/CD21(lo)) when compared with B cells with a classical memory (CD27(+)) or naive (CD27(-)/CD21(hi)) B cell phenotype. Tissuelike memory B cells expressed patterns of homing and inhibitory receptors similar to those described for antigen-specific T cell exhaustion. The tissuelike memory B cells proliferated poorly in response to B cell stimuli, which is consistent with high-level expression of multiple inhibitory receptors. Immunoglobulin diversities and replication histories were lower in tissuelike, compared with classical, memory B cells, which is consistent with premature exhaustion. Strikingly, HIV-specific responses were enriched in these exhausted tissuelike memory B cells, whereas total immunoglobulin and influenza-specific responses were enriched in classical memory B cells. These data suggest that HIV-associated premature exhaustion of B cells may contribute to poor antibody responses against HIV in infected individuals.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. smoir@niaid.nih.gov
authors.forename: Susan
authors.initials: S
authors.lastname: Moir
authors.forename: Jason
authors.initials: J
authors.lastname: Ho
authors.forename: Angela
authors.initials: A
authors.lastname: Malaspina
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Angela C
authors.initials: AC
authors.lastname: DiPoto
authors.forename: Marie A
authors.initials: MA
authors.lastname: O'Shea
authors.forename: Gregg
authors.initials: G
authors.lastname: Roby
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Michael A
authors.initials: MA
authors.lastname: Proschan
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology*; D016022:Case-Control Studies; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D018448:Models, Immunological; D010641:Phenotype; D011961:Receptors, Fc / Q000378:metabolism; D014766:Viremia / Q000276:immunology* / Q000821:virology; D014779:Virus Replication / Q000276:immunology
chemical_list: C423544:FCRL4 protein, human; D015483:HIV Antibodies; D011961:Receptors, Fc