B-cell abnormalities in HIV-1 infection roles for IgG3 and T-betKardava, Lela; Moir, SusanCurrent Opinion in HIV and AIDS: July 2019 - Volume 14 - Issue 4 - p 240–245 doi: 10.1097/COH.0000000000000547 BROAD NEUTRALISING AND NON-NEUTRALISING ANTIBODIES: Edited by Hugo Mouquet and Olivier Schwartz Buy Abstract Author InformationAuthors Article MetricsMetrics Purpose of review Numerous B-cell abnormalities in HIV-1 infection have been described over the past three decades yet have remained poorly defined mechanistically. We review recent studies that describe mechanisms of B-cell dysregulation in chronic HIV-1 infection associated with IgG3 and T-bet. Recent findings HIV-1 infection causes hypergammaglobulinemia and dysregulation of B-cell populations, including the expansion during chronic viremia of functionally impaired tissue-like memory (TLM) B cells. TLM B cells and B cells in other conditions of chronic activation and inflammation with similar phenotypes are characterized by increased expression of the transcription factor T-bet and preferential immunoglobulin class-switching to IgG3. However, defects in B-cell function during chronic HIV-1 viremia are also associated with the binding of soluble IgG3 to IgM-expressing B cells, with the highest intensities observed on TLM B cells. The consequence of IgG3 binding to TLM B cells is increased clustering of the IgM B-cell receptor and decreased response to stimulation. Summary The identification of T-bet and IgG3 as the regulators of B-cell function in chronic HIV-1 viremia could provide new targets for therapeutic intervention aimed at reversing the damaging effects of HIV-1-associated chronic immune activation. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA Correspondence to Susan Moir, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Tel: +1 301 402 4559; e-mail: firstname.lastname@example.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.