Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection.

Abstract

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-infected patients carry low levels of memory B cells. Here we studied whether defects in the naive and memory B cells in HIV-1-infected patients translated into hypergammaglobulinemia and defective humoral immunity against specific antigens. Naive B cells from HIV-1-infected 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-infected patients.

• Authors: Angelo De Milito, Anna Nilsson, Kehmia Titanji, Rigmor Thorstensson, Elisabet Reizenstein, Mitsuo Narita, Sven Grutzmeier, Anders Sönnerborg, Francesca Chiodi
• Journal: Blood (Blood) Vol. 103 Issue 6 Pg. 2180-6 (Mar 15 2004) ISSN: 0006-4971 [Print] United States
• PMID: 14604962 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• HIV Antibodies
• Immunoglobulin G
• Tetanus Toxoid

Topics

• Adult
• Antibodies, Viral (blood)
• Antibody Formation (immunology)
• B-Lymphocytes (immunology, metabolism, virology)
• Cell Communication (immunology)
• Female
• HIV Antibodies (blood)
• HIV Infections (complications, immunology)
• HIV-1 (immunology)
• Humans
• Hypergammaglobulinemia (immunology, virology)
• Immunoglobulin G (blood)
• Immunologic Memory (immunology)
• Immunophenotyping
• Male
• Measles (immunology)
• Middle Aged
• Tetanus Toxoid (immunology)