{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:39:32Z","timestamp":1791398372326,"version":"4.3.3"},"reference-count":32,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,8,4]]},"abstract":"<jats:p>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 (CD20hi\/CD27lo\/CD21lo) 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 (CD20hi\/CD27\u2212\/CD21lo) when compared with B cells with a classical memory (CD27+) or naive (CD27\u2212\/CD21hi) 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.<\/jats:p>","DOI":"10.1084\/jem.20072683","type":"journal-article","created":{"date-parts":[[2008,7,15]],"date-time":"2008-07-15T02:26:56Z","timestamp":1216088816000},"page":"1797-1805","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":840,"title":["Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals"],"prefix":"10.1084","volume":"205","author":[{"given":"Susan","family":"Moir","sequence":"first","affiliation":[{"name":"1Laboratory of Immunoregulation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Ho","sequence":"additional","affiliation":[{"name":"1Laboratory of Immunoregulation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Malaspina","sequence":"additional","affiliation":[{"name":"1Laboratory of Immunoregulation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"1Laboratory of Immunoregulation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela C.","family":"DiPoto","sequence":"additional","affiliation":[{"name":"1Laboratory of Immunoregulation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie A.","family":"O'Shea","sequence":"additional","affiliation":[{"name":"1Laboratory of Immunoregulation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg","family":"Roby","sequence":"additional","affiliation":[{"name":"1Laboratory of Immunoregulation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Kottilil","sequence":"additional","affiliation":[{"name":"1Laboratory of Immunoregulation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Arthos","sequence":"additional","affiliation":[{"name":"1Laboratory of Immunoregulation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Proschan","sequence":"additional","affiliation":[{"name":"2Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Wook","family":"Chun","sequence":"additional","affiliation":[{"name":"1Laboratory of Immunoregulation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony S.","family":"Fauci","sequence":"additional","affiliation":[{"name":"1Laboratory of Immunoregulation"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2008,7,14]]},"reference":[{"key":"2023072916141704000_BIB1","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1189\/jlb.0306157","volume":"80","year":"2006","journal-title":"J. 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