Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals

J Exp Med. 2008 Aug 4;205(8):1797-805. doi: 10.1084/jem.20072683. Epub 2008 Jul 14.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / virology*
  • Case-Control Studies
  • HIV Antibodies / biosynthesis
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Immunologic Memory*
  • Lymphocyte Activation
  • Models, Immunological
  • Phenotype
  • Receptors, Fc / metabolism
  • Viremia / immunology*
  • Viremia / virology
  • Virus Replication / immunology


  • FCRL4 protein, human
  • HIV Antibodies
  • Receptors, Fc