Direct Polyclonal Activation of Human B Lymphocytes by the Acquired Immune Deficiency Syndrome Virus

Schnittman, S M; Lane, H. Clifford; Higgins, SE; Folks, Thomas M.; As, Fauci

doi:10.1126/science.3016902

Cited by 342 publications

(136 citation statements)

References 19 publications

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…Several mechanisms have been suggested for excessive B cell activation in HIV-1 disease, including the direct stimulatory effects of viral proteins on B cells and induction of B cell stimulatory cytokines associated with HIV-1 infection (25). In addition, enhanced T cell help has been implicated in the induction of polyclonal B cell activation (45,46). It has been demonstrated that the envelope glycoproteins induce differentiation of B lymphocytes from normal volunteers into Ig-secreting cells (20,25).…”

Section: Discussionmentioning

confidence: 99%

Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy

Popovič

Tenner-Rácz

Pelser

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

152

125

View full text Add to dashboard Cite

Here we report a long-term persistence of HIV-1 structural proteins and glycoproteins in germinal centers (GCs) of lymph nodes (LNs) in the absence of detectable virus replication in patients under highly active antiretroviral therapy (HAART). The persistence of viral structural proteins and glycoproteins in GCs was accompanied by specific antibody responses to HIV-1. Seven patients during the chronic phase of HIV-1 infection were analyzed for the presence of the capsid protein (HIV-1p24), matrix protein (HIV-1p17), and envelope glycoproteins (HIV-1gp120͞gp41), as well as for viral RNA (vRNA) in biopsy specimens from LNs obtained before initiation of therapy and during HAART that lasted from 5 to 13 months. In parallel, these patients were also monitored for viremia and specific anti-HIV-1 antibody responses to structural proteins and glycoproteins both before and during treatment. Before-therapy viral levels, as determined by RT-PCR, ranged from 3 ؋ 10 3 to 6.3 ؋ 10 5 copies of vRNA per ml, whereas during treatment, vRNA was under detectable levels (<25 copies per ml). The pattern of vRNA detection in peripheral blood was concordant with in situ hybridization results of LN specimens. Before treatment, vRNA associated with follicular dendritic cells (FDCs) was readily detected in GCs of LNs of the patients, whereas during therapy, vRNA was consistently absent in the GCs of LN biopsies of treated patients. In contrast to vRNA hybridization results, viral structural proteins and glycoproteins, evaluated by immunohistochemical staining, were present and persisted in the GC light zone of LNs in abundant amounts not only before initiation of therapy but also during HAART, when no vRNA was detected in GCs. Consistent with immunohistochemical findings, specific antibody responses to HIV1p17, -p24, and -gp120͞gp41, as evaluated by ELISA and virus neutralization, persisted in patients under therapy for up to 13 months of follow-up. The implications of these findings are discussed in relation to HIV-1 persistence in infected individuals and the potential role of chronic antigenic stimulation by the deposited structural proteins in GCs for AIDS-associated B cell malignancies.

show abstract

Section: Discussionmentioning

confidence: 99%

Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy

Popovič

Tenner-Rácz

Pelser

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

152

125

View full text Add to dashboard Cite

show abstract

“…4,82 The broad activation of B lymphocytes in HIV infection is wellcharacterized. [3][4][5][7][8][9] This B cell activation, with the expansion of EBV-infected B cell populations, may be the initial steps in B lineage tumorigenesis and may account for the high frequency of oligoclonal lymphoma observed in these patients. 5 Such a broad lymphocyte activation may predispose to the generation of lymphoma even in the absence of EBV infection.…”

Section: Gammopathy and Plasma Cell Tumors In Aidsmentioning

confidence: 99%

“…3,5 B cells exposed to HIV in vitro may proliferate 6 or become activated and begin secreting immunoglobulin. 4,7,8 HIV-infected T cells can induce contact-dependent but antigen-independent polyclonal activation of B cells. 9 Bone marrow biopsy of HIV-infected patients commonly reveals a plasmacytosis, even in the absence of any plasma cell disorder.…”

Section: Introductionmentioning

confidence: 99%

Paraproteinemia, plasmacytoma, myeloma and HIV infection

Fiorino

Atac

1997

Leukemia

View full text Add to dashboard Cite

We have identified by MEDLINE search the cases of gammaglobinopathy and plasma cell malignancy in HIV-positive patients reported in the English language literature. The average age at presentation among HIV-positive patients with plasma cell disorders is 33 years, far younger than the average age of presentation in the general population. Some of these patients present with transient paraproteinemias, while others have persistent paraproteins, which may or may not be associated with true plasma cell malignancies. In most cases in which it has been examined, the paraprotein contains high-titer anti-HIV activity. The presence of high-titer anti-HIV activity in the paraproteins of AIDS patients suggests that an antigen-driven process in response to HIV infection may contribute to the early development of plasma cell disorders in these patients. Recent work in plasma cell tumorigenesis has indicated that transformation at a single point in the B lymphocyte lineage can give rise to either lymphoma or myeloma, dependent upon environmental factors such as T cell function, which may be required for directing transformed lymphocytes from lymphoma and towards plasma cell differentiation. This may explain why B lineage oncogenesis in AIDS patients favors the development of lymphoma over that of myeloma.

show abstract

“…HIV infection induces a vigorous immune response with a 10-fold increase in polyclonal immunoglobulin production. Polyclonal B cell activation by HIV may be a direct mitogenic effect or may be antigenspecific (Schnittman et al, 1986). Parasite induced T cell immunosuppression and polyclonal B-cell activation are thus features of both HIV and malaria infection and suggests that HIV infection may be performing an analogous role to holoendemic malaria in the pathogenesis of BL.…”

Section: Burkitt's Lymphomamentioning

confidence: 99%

The biology of HIV-associated lymphomas

Bower¹

1992

Br J Cancer

View full text Add to dashboard Cite

Direct Polyclonal Activation of Human B Lymphocytes by the Acquired Immune Deficiency Syndrome Virus

Cited by 342 publications

References 19 publications

Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy

Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy

Paraproteinemia, plasmacytoma, myeloma and HIV infection

The biology of HIV-associated lymphomas

Contact Info

Product

Resources

About