HIV-1 induces phenotypic and functional perturbations of B cells in chronically infected individuals

A number of perturbations of B cells has been described in the setting of HIV infection; however, most remain poorly understood. To directly address the effect of HIV replication on B cell function, we investigated the capacity of B cells isolated from HIV-infected patients to respond to a variety of stimuli before and after reduction of viremia by effective antiretroviral therapy. B cells taken from patients with high levels of plasma viremia were defective in their proliferative responses to various stimuli. Viremia was also associated with the appearance of a subpopulation of B cells that expressed reduced levels of CD21. After fractionation into CD21high- and CD21low-expressing B cells, the CD21low fraction showed dramatically reduced proliferation in response to B cell stimuli and enhanced secretion of immunoglobulins when compared with the CD21high fraction. Electron microscopic analysis of each fraction revealed cells with plasmacytoid features in the CD21low B cell population but not in the CD21high fraction. These results indicate that HIV viremia induces the appearance of a subset of B cells whose function is impaired and which may be responsible for the hypergammaglobulinemia associated with HIV disease.

[1]  F. Chiodi,et al.  Loss of memory (CD27) B lymphocytes in HIV-1 infection , 2001, AIDS.

[2]  P. Lipsky,et al.  Disturbed Peripheral B Lymphocyte Homeostasis in Systemic Lupus Erythematosus1 , 2000, The Journal of Immunology.

[3]  H. Peter,et al.  Reduced expression of the complement receptor type 2 (CR2, CD21) by synovial fluid B and T lymphocytes , 2000, Clinical and experimental immunology.

[4]  T. Chun,et al.  B Cells of HIV-1–Infected Patients Bind Virions through Cd21–Complement Interactions and Transmit Infectious Virus to Activated T Cells , 2000, The Journal of experimental medicine.

[5]  G. Gaidano,et al.  The molecular basis of acquired immunodeficiency syndrome-related lymphomagenesis. , 2000, Seminars in oncology.

[6]  R. Detels,et al.  Aberrant expression of CD27 and soluble CD27 (sCD27) in HIV infection and in AIDS-associated lymphoma. , 1999, Clinical immunology.

[7]  R. Freeman,et al.  Epstein-Barr Virus–Infected Resting Memory B Cells, Not Proliferating Lymphoblasts, Accumulate in the Peripheral Blood of Immunosuppressed Patients , 1999, The Journal of experimental medicine.

[8]  H. Takamatsu,et al.  African swine fever virus: a B cell-mitogenic virus in vivo and in vitro. , 1999, The Journal of general virology.

[9]  K. Tarte,et al.  Impairment of B‐lymphocyte differentiation induced by dual triggering of the B‐cell antigen receptor and CD40 in advanced HIV‐1‐disease , 1998, AIDS.

[10]  D. Ho,et al.  HIV-1 Antigen–specific and –nonspecific B Cell Responses Are Sensitive to Combination Antiretroviral Therapy , 1998, The Journal of experimental medicine.

[11]  M. Dehoff,et al.  An intronic silencer regulates B lymphocyte cell- and stage-specific expression of the human complement receptor type 2 (CR2, CD21) gene. , 1998, Journal of immunology.

[12]  V. M. Holers,et al.  Mouse complement receptors type 1 (CR1;CD35) and type 2 (CR2;CD21): expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL/lpr mice. , 1997, Journal of immunology.

[13]  G. Kelsoe,et al.  Antibody response to a T-dependent antigen requires B cell expression of complement receptors , 1996, The Journal of experimental medicine.

[14]  J. Ahearn,et al.  Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen. , 1996, Immunity.

[15]  J. Banchereau,et al.  Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts , 1996, The Journal of experimental medicine.

[16]  W. Cumberland,et al.  Elevated serum levels of soluble CD23 (sCD23) precede the appearance ofacquired immunodeficiency syndrome--associated non-Hodgkin's lymphoma. , 1995, Blood.

[17]  A Schwartz,et al.  Development of Clinical Standards for Flow Cytometry , 1993, Annals of the New York Academy of Sciences.

[18]  F. Barré-Sinoussi,et al.  HIV induces IL-6 production by human B lymphocytes. Role of IL-4. , 1992, Journal of immunology.

[19]  N. Chirmule,et al.  Inhibition of normal B-cell function by human immunodeficiency virus envelope glycoprotein, gp120. , 1992, Blood.

[20]  D. Klinman,et al.  Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation. , 1992, The Journal of clinical investigation.

[21]  A. di Caro,et al.  Identification of a CD21 receptor-deficient, non-Ig-secreting peripheral B lymphocyte subset in HIV-seropositive drug abusers. , 1992, Clinical immunology and immunopathology.

[22]  J. Delfraissy,et al.  Tumor necrosis factor-alpha inhibits the competence signal delivered by HIV to normal B cells. , 1991, Journal of immunology.

[23]  P. von Wichert,et al.  Expression of CD 21, CD 22, and the mouse erythrocyte receptor on peripheral B lymphocytes in rheumatoid arthritis. , 1988, Annals of the rheumatic diseases.

[24]  M. Lathrop,et al.  Impaired anti-pneumococcal antibody response in patients with AIDS-related persistent generalized lymphadenopathy. , 1987, Clinical and experimental immunology.

[25]  J. Fahey,et al.  Infection with the human immunodeficiency virus (HIV) is associated with an in vivo increase in B lymphocyte activation and immaturity. , 1987, Journal of immunology.

[26]  A. Fauci,et al.  Direct polyclonal activation of human B lymphocytes by the acquired immune deficiency syndrome virus. , 1986, Science.

[27]  B. Safai,et al.  Antigen-specific and polyclonal B-cell responses in patients with acquired immunodeficiency disease syndrome. , 1986, Clinical immunology and immunopathology.

[28]  P. Schur,et al.  Decreased expression of the C3b/C4b receptor (CR1) and the C3d receptor (CR2) on B lymphocytes and of CR1 on neutrophils of patients with systemic lupus erythematosus. , 1986, Arthritis and rheumatism.

[29]  H. Ochs,et al.  Defective humoral immunity in pediatric acquired immune deficiency syndrome. , 1985, The Journal of pediatrics.

[30]  M. Grieco,et al.  Defective B-lymphocyte function in homosexual men in relation to the acquired immunodeficiency syndrome. , 1984, Annals of internal medicine.

[31]  M. Cooper,et al.  Expression of C3d receptors during human B cell differentiation: immunofluorescence analysis with the HB-5 monoclonal antibody. , 1984, Journal of immunology.

[32]  P. Volberding,et al.  B-cell immunodeficiency in acquired immune deficiency syndrome. , 1984, JAMA.

[33]  A. Fauci,et al.  Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. , 1983, The New England journal of medicine.

[34]  Mark G. Lewis,et al.  Enhanced Follicular Dendritic Cell-B Cell Interaction in HIV and SIV Infections and its Potential Role in Polyclonal B Cell Activation , 1998, Developmental immunology.

[35]  T. Lint,et al.  In vivo decrease in the expression of complement receptor 2 on B-cells in HIV infection. , 1993, AIDS.

[36]  E. Reinherz,et al.  Immunoregulatory subsets of the T helper and T suppressor cell populations in homosexual men with chronic unexplained lymphadenopathy. , 1984, The Journal of clinical investigation.