In Vitro Response to HBsAg of Peripheral Blood Lymphocytes from Recipients of Hepatitis B Vaccine

Chang, Tse Wen; Celis, Esteban; Miller, Richard W.; Zurawski, Vincent R.; Kung, Patrick

doi:10.1002/hep.1840040504

Cited by 16 publications

(8 citation statements)

References 25 publications

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“…Recently it was shown by ELISPOT that oral vaccination with the cholera toxin B (CT-B) evokes a long-lasting enrichment of anti-CT-B-producing B cells in the intestinal lymphoid tissue, whereas in the peripheral blood lower specific B cell frequencies were detectable for a short time [28]. In concordance with these data we demonstrated a high frequency of anti-HBs-producing B cells shortly after the onset of acute hepatitis B, and low frequencies years after viral clearance or vaccination [21][22][23][24][25][26][27][28][29]. Future studies will have to clarify whether patients with acute self-limited HBV infection can be distinguished from chronic HBV carriers in the early phase of hepatitis by the numbers of SFC.…”

Section: Discussionsupporting

confidence: 79%

“…1% HEPES buffer and 0 . 1% gentamycine in 24-well flat-bottomed plates (Falcon/Becton Dickinson, Heidelberg, Germany) for 8-10 days in a humified atmosphere with 5% CO 2 at 378C [20,21]. The supernatants were harvested, filtered and stored at ÿ 208C before anti-HBs antibodies were determined using the commercially available assay (AUSAB EIA; Abbott Labs, Wiesbaden, Germany).…”

Section: Anti-hbs Secretion In Cell Culture Supernatantsmentioning

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: Discussionsupporting

confidence: 79%

Section: Anti-hbs Secretion In Cell Culture Supernatantsmentioning

confidence: 99%

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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“…In this type of assay, the in vitro HBsAg-induced production of anti-HBs by autologous B cells in the absence of mitogens was determined. The concentration of HBsAg chosen for this study (10 ng per ml) was previously shown to be optimal for in vitro antiHBs production (14,16). The results in Table 1 show that in only one of the triplicate samples significant synthesis of anti-HBs was observed when T cells, B cells and HBsAg were present simultaneously.…”

Section: Resultsmentioning

confidence: 99%

“…Again, the presence of both helper T cells and antigen (HBsAg) were required in order to observe the enhancing effect of the anti-HBs of IgG class in the production of antigen-specific antibodies. A large degree of variation was observed between the triplicate samples in this assay, which is probably a reflection of the limiting number of HBsAg-specific B lymphocytes present in each culture (14,16). Experiments presented here also indicate that the in vivo antibody response to HBsAg can be regulated by anti-HBs.…”

Section: (75)mentioning

confidence: 99%

Modulation of the immunological response to hepatitis b virus by antibodies

1987

Self Cite

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Antibodies to HBsAg of IgG class enhanced the helper activity of a human T cell clone to promote the in vitro synthesis of immunoglobulins by autologous B lymphocytes. Using two different assay systems, the effect of antigen-specific antibodies on the helper function of a HBsAg-reactive T cell clone was studied. The monoclonal antibody to HBsAg A5C3 (IgG) increased significantly the T cell-dependent production of immunoglobulins by Staphyloccocus aureus-stimulated autologous B lymphocytes. Furthermore, the results obtained with a different type of assay showed that A5C3 also increased the synthesis of antibody to HBsAg by the autologous B cells in the presence of HBsAg and the helper T cell clone. On the other hand, when the monoclonal antibody to HBsAg of IgM class, H5D3 or the F(ab')2 fragment of A5C3 were tested, no significant enhancement of the helper activity of the T cell clone was observed. Experiments performed in mice showed that the in vivo antibody to HBsAg response to low concentrations of HBsAg was significantly enhanced by mixing this antigen with monoclonal antibody to HBsAg of IgG class. No effect was observed when a monoclonal antibody to HBsAg of IgM class was used to prepare the immune-complexed immunogen. The results presented here suggest that antibodies play a critical role in their own production through regulating the activity of helper T cells. This phenomenon might contribute to the increased antibody synthesis of in vivo secondary immune responses and could be of use in designing more efficient vaccine programs in man.

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“…It was shown, in mice and man [4,5], that synthesis of these antibodies is regulated by T lymphocytes (T‐dependent HBsAg). Furthermore, a close correlation between the in vivo humoral and the in vitro cellular responses to HBsAg has been demonstrated in HB vaccine recipients [6] and in patients with acute HBV infections [7].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the T cell recognition of hepatitis B surface antigen (HBsAg) by good and poor responders to hepatitis B vaccines

Desombere

Gijbels

Verwulgen

et al. 2000

Clinical and Experimental Immunology

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SUMMARYTo study the regulation of the human cellular immune response to HBsAg we produced a series of HBsAg-specific T cell lines from good and poor responders to the hepatitis B vaccine. All T cell lines expressed CD4 on their membrane and could therefore be considered of the helper/inducer phenotype. The different HBsAg-specific T cell lines were restricted by HLA-DRB5*0101, DRB1*1201, -DRB1*0701, -DRB1*0301, -DPB1*0201, -DPB1*0402, and -DPB1*0901. In good responders to the hepatitis B vaccine different HLA molecules could act as restricting element. In poor responders the diversity of HLA class II restriction determinants was more limited. This leads us to conclude that the immune response to HBsAg is multispecific and polyclonal in good responders and paucispecific and oligoclonal in poor responders to the hepatitis B vaccine. By using a panel of synthetic peptides representing selected sequences of the HBsAg, the fine specificities of each of these T cell lines could be determined. Strikingly, the majority of the identified T cell epitopes was located in and around the first hydrophobic transmembranous region of the HBsAg. This was observed in T cell lines from good and poor vaccine responders, without distinction. The remarkable T cell immunogenicity of this region may reside in its richness in binding motifs for a variety of HLA class II determinants.

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In Vitro Response to HBsAg of Peripheral Blood Lymphocytes from Recipients of Hepatitis B Vaccine

Cited by 16 publications

References 25 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

Modulation of the immunological response to hepatitis b virus by antibodies

Characterization of the T cell recognition of hepatitis B surface antigen (HBsAg) by good and poor responders to hepatitis B vaccines

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