{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:33:06Z","timestamp":1791282786788,"version":"4.1.0"},"reference-count":55,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypergammaglobulinemia and defective humoral immunity are hallmarks of HIV-1 infection. Naive B cells have been recently suggested as the major source of hypergammaglobulinemia in chronic viral infections. We recently reported that HIV-1\u2013infected patients carry low levels of memory B cells. Here we studied whether defects in the naive and memory B cells in HIV-1\u2013infected patients translated into hypergammaglobulinemia and defective humoral immunity against specific antigens. Naive B cells from HIV-1\u2013infected patients exhibited abnormal expression of the activation\/differentiation markers CD70 and leukocyte-associated Ig-like receptor (LAIR-1). Activated naive B cells from patients showed a significant increase in the intracellular immunoglobulin G (IgG) content ex vivo and this activated phenotype correlated to hypergammaglobulinemia and to the ability of naive B cells from patients to secrete IgG in vitro. We analyzed the levels of antibodies to tetanus toxoid, measles, and HIV-1 in relation to memory B cells and observed a significant reduction of antigen-specific antibodies in patients with low-memory B lymphocytes. Nevertheless, hypergammaglobulinemia and levels of polyspecific self-reactive antibodies were comparable in patients with normal and low memory B cells. We conclude that reduction of memory B lymphocytes in HIV-1 infection correlates with defective humoral immunity and that hyperactivated naive B cells may represent the source of abnormal IgG production in HIV-1 infection. Our results may be relevant to the design of HIV-1 therapeutical vaccines and to the clinical management of HIV-1\u2013infected patients.<\/jats:p>","DOI":"10.1182\/blood-2003-07-2375","type":"journal-article","created":{"date-parts":[[2003,11,11]],"date-time":"2003-11-11T01:13:36Z","timestamp":1068513216000},"page":"2180-2186","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":258,"title":["Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection"],"prefix":"10.1182","volume":"103","author":[{"given":"Angelo","family":"De Milito","sequence":"first","affiliation":[{"name":"From the Microbiology and Tumor Biology Center, Karolinska Institutet, and the Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden; the Swedish Institute for Infectious Disease Control, Solna, Sweden; the Department of Pediatrics, Hokkaido University, Sapporo, Japan; and the Division of Clinical Virology, Department of Immunology, Microbiology, and Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Nilsson","sequence":"additional","affiliation":[{"name":"From the Microbiology and Tumor Biology Center, Karolinska Institutet, and the Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden; the Swedish Institute for Infectious Disease Control, Solna, Sweden; the Department of Pediatrics, Hokkaido University, Sapporo, Japan; and the Division of Clinical Virology, Department of Immunology, Microbiology, and Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kehmia","family":"Titanji","sequence":"additional","affiliation":[{"name":"From the Microbiology and Tumor Biology Center, Karolinska Institutet, and the Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden; the Swedish Institute for Infectious Disease Control, Solna, Sweden; the Department of Pediatrics, Hokkaido University, Sapporo, Japan; and the Division of Clinical Virology, Department of Immunology, Microbiology, and Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rigmor","family":"Thorstensson","sequence":"additional","affiliation":[{"name":"From the Microbiology and Tumor Biology Center, Karolinska Institutet, and the Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden; the Swedish Institute for Infectious Disease Control, Solna, Sweden; the Department of Pediatrics, Hokkaido University, Sapporo, Japan; and the Division of Clinical Virology, Department of Immunology, Microbiology, and Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Reizenstein","sequence":"additional","affiliation":[{"name":"From the Microbiology and Tumor Biology Center, Karolinska Institutet, and the Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden; the Swedish Institute for Infectious Disease Control, Solna, Sweden; the Department of Pediatrics, Hokkaido University, Sapporo, Japan; and the Division of Clinical Virology, Department of Immunology, Microbiology, and Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuo","family":"Narita","sequence":"additional","affiliation":[{"name":"From the Microbiology and Tumor Biology Center, Karolinska Institutet, and the Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden; the Swedish Institute for Infectious Disease Control, Solna, Sweden; the Department of Pediatrics, Hokkaido University, Sapporo, Japan; and the Division of Clinical Virology, Department of Immunology, Microbiology, and Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Grutzmeier","sequence":"additional","affiliation":[{"name":"From the Microbiology and Tumor Biology Center, Karolinska Institutet, and the Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden; the Swedish Institute for Infectious Disease Control, Solna, Sweden; the Department of Pediatrics, Hokkaido University, Sapporo, Japan; and the Division of Clinical Virology, Department of Immunology, Microbiology, and Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"So\u0308nnerborg","sequence":"additional","affiliation":[{"name":"From the Microbiology and Tumor Biology Center, Karolinska Institutet, and the Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden; the Swedish Institute for Infectious Disease Control, Solna, Sweden; the Department of Pediatrics, Hokkaido University, Sapporo, Japan; and the Division of Clinical Virology, Department of Immunology, Microbiology, and Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Chiodi","sequence":"additional","affiliation":[{"name":"From the Microbiology and Tumor Biology Center, Karolinska Institutet, and the Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden; the Swedish Institute for Infectious Disease Control, Solna, Sweden; the Department of Pediatrics, Hokkaido University, Sapporo, Japan; and the Division of Clinical Virology, Department of Immunology, Microbiology, and Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021221493078300_REF1","doi-asserted-by":"crossref","unstructured":"De Milito A. 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