B-cell exhaustion in HIV infection: the role of immune activationMoir, Susan; Fauci, Anthony S.Current Opinion in HIV & AIDS: September 2014 - Volume 9 - Issue 5 - p 472–477 doi: 10.1097/COH.0000000000000092 CELL EXHAUSTION IN HIV-1 INFECTION: Edited by Daniel E. Kaufmann and Nabila Seddiki Abstract Author Information Purpose of review: To discuss a component of the pathogenic mechanisms of HIV infection in the context of phenotypic and functional alterations in B cells that are due to persistent viral replication leading to aberrant immune activation and cellular exhaustion. We explore how B-cell exhaustion arises during persistent viremia and how it compares with T-cell exhaustion and similar B-cell alterations in other diseases. Recent findings: HIV-associated B-cell exhaustion was first described in 2008, soon after the demonstration of persistent virus-induced T-cell exhaustion, as well as the identification of a subset B cells in tonsil tissues with immunoregulatory features similar to those observed in T-cell exhaustion. Our understanding of B-cell exhaustion has since expanded in two important areas: the role of inhibitory receptors in the unresponsiveness of exhausted B cells and the increasing evidence that similar B cells are found in other diseases that are associated with aberrant immune activation and inflammation. Summary: The phenomenon of B-cell exhaustion is now well established in HIV infection and other diseases characterized by immune activation. Over the coming years, it will be important to understand how cellular exhaustion affects the capacity of the immune system to respond to persisting primary pathogens, as well as to other microbial antigens, whether encountered as secondary infections or following immunization. Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, USA Correspondence to Susan Moir, Laboratory of Immunoregulation, NIAID/NIH, Building 10, Room 6A02, 9000 Rockville Pike, Bethesda, MD 20892, USA. Tel: +1 301 402 4559; fax: +1 301 480 0643; e-mail: firstname.lastname@example.org © 2014 Lippincott Williams & Wilkins, Inc.