Synthesis of antibodies to hepatitis B virus by cultured lymphocytes from chronic hepatitis B surface antigen carriers.

Dusheiko, G.; Hoofnagle, Jay H.; Cooksley, W. G. E.; James, Stephen P.; Jones, E. Anthony

doi:10.1172/jci110860

Cited by 71 publications

(47 citation statements)

References 28 publications

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“…Cocultures of B cells derived from vaccine recipients together with autologous or allogeneic HLA-class II-matched ormismatched T cell preparations resulted in a strong increase of HBs-specific SFC. Thus, it could be confirmed that anti-HBs antibody formation is dependent on the presence of T cells but not restricted to identical HLA molecules [12,13,25,30]. It can be speculated that this T cell help is mediated by alloreactive T cell stimulation followed by the release of cytokines or the expression of adhesion molecules.…”

Section: Regulation Of Anti-hbs Immune Response In Vitro 55mentioning

confidence: 93%

“…In addition, an association of the HLA class II allele DRB1*1302 with protection against persistent HBV infection was shown [11]. Recent studies have suggested defective T and B cell functions [12,13]. A general problem of these studies was the low sensitivity of the in vitro assays used to detect HBs-specific antibody production [12].…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have suggested defective T and B cell functions [12,13]. A general problem of these studies was the low sensitivity of the in vitro assays used to detect HBs-specific antibody production [12]. Thus, the aims of our study were: (i) to establish a sensitive in vitro assay for the detection of anti-HBsproducing B cells; (ii) to analyse the HBs-specific humoral immune responses in vaccine recipients, HBV-immunized individuals and patients with acute or chronic HBV infection; (iii) to correlate HBs-specific humoral and cellular immune responses; and (iv) to study the T cell dependence of anti-HBs production in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection

Böcher

Herzog-Hauff

Herr

et al. 1996

Clinical and Experimental Immunology

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SUMMARYAntibodies directed to the HBs antigen indicate viral clearance and the development of life-long immunity in patients that recovered from HBV infection. In HBs antigen vaccine recipients anti-HBs antibodies provide protective immunity. However, little is known about the regulation of this HBsspecific antibody response. The existence of anti-HBs-secreting B cells was demonstrated using the highly sensitive ELISPOT technique compared with conventional ELISA in serum and cell culture supernatants. In the peripheral blood of patients with acute self-limited hepatitis B, HBs-specific B cells were demonstrated with a high frequency despite undetectable anti-HBs serum antibodies. HBVimmunized patients that had recovered from infection and vaccine recipients had significantly lower frequencies, whereas chronic HBV carriers and negative controls showed no anti-HBs-secreting B cells. Coculture experiments of isolated B and T cells revealed that the anti-HBs antibody response was restricted to the presence of T helper cells, but not to identical HLA class II molecules. Allogeneic T cells derived from vaccine recipients or chronic HBV carriers stimulated the HBs-specific B cell response in HBs vaccine recipients. Otherwise, isolated T helper cells could never provide sufficient help to induce the HBs-specific B cell response in chronic HBV carriers. Furthermore, peripheral blood mononuclear cells (PBMC) of six out of 10 vaccine recipients, one out of five HBV-immunized patients, but of no chronic HBV carrier showed a proliferative response to different HBs antigen preparations. This study demonstrated a high frequency of circulating anti-HBs-producing B cells in the early phase of acute HBV infection, but a lower frequency of HBs-specific B cells years after resolution of HBV infection. In chronic HBV carriers, however, deficient HBs-specific T and B cell responses were observed.

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Section: Regulation Of Anti-hbs Immune Response In Vitro 55mentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection

Böcher

Herzog-Hauff

Herr

et al. 1996

Clinical and Experimental Immunology

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“…This is in accordance with previous reports of a defect in anti-HBs antibody production of PBMC derived from chronic HBV patients. 29 In apparent contradiction to these data, a recent study described the existence of antienvelope antibodies in immune complexes in sera of the majority of CHB patients by the use of more sensitive assays. 8 However, these antibodies have nei- ther been compared with the titers of individuals who had recovered from HBV infection or been characterized in terms of epitope specificity (i.e., preS or HBs).…”

Section: Discussionmentioning

confidence: 97%

“…29 However, in more recent studies, the existence of antienvelope antibodies in immune complexes was shown in sera of patients with CHB, arguing for a merely quantitative defect in anti-HBs antibody secretion. 8 Using a novel chimeric mouse model, our report shows the dependence of the human anti-HBs response on the activation of HBs-specific Th1 cells.…”

Section: Discussionmentioning

confidence: 99%

Reduced hepatitis B virus surface antigen-specific Th1 helper cell frequency of chronic HBV carriers is associated with a failure to produce antigen-specific antibodies in the Trimera mouse

et al. 2000

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In chronic hepatitis B virus (HBV) infectionInfection with the hepatitis B virus (HBV) is one of the most common infectious diseases with an estimated 300 million chronic HBV carriers worldwide. 1 The high risk of patients with chronic hepatitis B (CHB) developing liver cirrhosis and hepatocellular carcinoma is associated with a high morbidity and mortality. Because HBV is a noncytopathic virus, liver injury is mainly mediated by the host immune response against virus-infected liver cells. 2 Strong HBV core/precore (HBc/e) specific T helper (Th) cell activities are detectable in acute self-limited hepatitis B or during exacerbations of the chronic disease in concert with strong HBV envelope, core, and polymerase-specific cytotoxic T lymphocyte reactivities, whereas such T-cell responses are weak in chronic disease. [3][4][5][6] This HBV-specific T-cell failure of chronic HBV carriers is believed to account for viral persistence.Furthermore, the B-and Th-cell response to the HBV surface antigen (HBsAg) seems to be insufficient in chronic hepatitis B. Whereas in patients with acute hepatitis B, the disappearance of HBsAg and the occurrence of anti-hepatitis B surface antigen (HBs) antibodies in serum mark viral elimination with subsequent development of protective immunity, in patients with CHB such antibodies are usually undetectable. Accordingly, low frequencies of anti-HBssecreting B cells are detected in the latter patients in contrast to very high B-cell numbers in patients with acute self-limited hepatitis B. 7 However, from current in vitro studies it remains unclear whether chronic HBV carriers exhibit an HBsAgspecific Th cell defect because proliferative T-cell responses to HBsAg are very weak or undetectable not only in chronic infection but also during acute hepatitis B or during acute exacerbations of the chronic disease. 4,5 Moreover, in a recent study, antienvelope antibodies were detected in immune complexes with HBsAg in sera of patients with chronic HBV infection. 8 However, the epitope specificity of such antibodies was not further specified (i.e., anti-preS1/2 or anti-HBs) and the antibody levels were not compared with those of HBVimmunized or HBs-vaccinated individuals. Thus, our current knowledge about the cellular and molecular mechanisms of the presumed HBs-specific B-and T-cell defect of chronic HBV carriers is controversial and limited.Anti-HBs antibodies might mediate important antiviral effector functions because anti-HBs antibodies are virus neutralizing, 9,10 HBsAg is expressed on the membrane of infected liver cells 11 and anti-HBs-mediated cytotoxicity has

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Viral Hepatitis

Rizzetto¹,

Zoulim²

2007

Textbook of Hepatology

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Synthesis of antibodies to hepatitis B virus by cultured lymphocytes from chronic hepatitis B surface antigen carriers.

Cited by 71 publications

References 28 publications

Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection

Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection

Reduced hepatitis B virus surface antigen-specific Th1 helper cell frequency of chronic HBV carriers is associated with a failure to produce antigen-specific antibodies in the Trimera mouse

Viral Hepatitis

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