In vitro antigen-induced antibody responses to hepatitis B surface antigen in man. Kinetic and cellular requirements.

Cupps, Thomas R.; Gerin, John L.; Purcell, R H; Goldsmith, Paul K.; Fauci, Anthony S.

doi:10.1172/jci111529

Cited by 27 publications

(9 citation statements)

References 41 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: Discussionmentioning

confidence: 93%

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: Discussionmentioning

confidence: 93%

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 other reports, peripheral blood cells from hyperimmunized individuals synthesized anti-HBs in vitro, although there was no cell-mediated hypersensitivity or T cell proliferative response to HBsAg (45,46) . In another study, nonresponders to HBsAg had significantly higher absolute and relative numbers of CD2+ (T11+), CD57+ (HNK-1+), and CD8* (T8+) lymphocytes and increased numbers of suppressor lymphocytes (47). Cell coculture experiments suggested that the early stage of nonresponsiveness is mainly due to a defect in the B cell repertoire, while the later stage is caused by HBsAg-specific suppressor T cells (48).…”

Section: Discussionmentioning

confidence: 97%

The cellular basis for lack of antibody response to hepatitis B vaccine in humans.

Egea

Iglesias

Salazar

et al. 1991

The Journal of Experimental Medicine

120

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SummaryWe had previously obtained evidence that among normal subjects the humoral antibody response to hepatitis B surface antigen (HBsAg) was bimodally distributed with about 14% of subjects producing <1,000 estimated radioimmunoassay RIA units . From the study of major histocompatibility complex (MHC) markers in the very poor responders who produced <36 estimated RIA units of antibody, it appeared that there was an excess of homozygotes for two extended haplotypes [HLAB8, SC01, DR3] and FC31, DR7] . This finding suggested that a poor response was inherited as a recessive trait requiring nonresponse genes for HBsAg on both MHC haplotypes and was strengthened by finding a much lower antibody response among prospectively immunized homozygotes for [HLAB8, SCOT, DR3] compared with heterozygotes . In the present study, we have analyzed the cellular basis for nonresponse to this antigen by examining antigen-specific proliferation of T cells from responders and nonresponders in the presence and absence of autologous CD8+ (suppressor) cells .Peripheral blood cells from nonresponders to HB&Ag failed to undergo a proliferative response to recombinant HB&Ag in vitro, whereas cells from responders proliferated vigorously. This failure of cells from nonresponders to proliferate was not reversed in cell mixtures containing CD4+ and antigen-presenting cells devoid of CD8+ cells . There was no difference between responders and nonresponders with respect to the number of circulating T cells or their subsets, or the proliferative response to mitogens such as pokeweed or phytohemagglutinin or another antigen, tetanus toxoid.Our results indicate that our HBsAg nonresponding subjects have a very specific failure in antigen presentation or the stimulation of T helper cells, or both. Our evidence is against specific immune suppression as the basis for their nonresponsiveness. The failure of antigen presentation or T cell help is consistent with recessive inheritance of nonresponsiveness and suggests that response is dominantly inherited .T he humoral antibody response to protein antigens is controlled by class II MHC genes in the mouse and other mammalian species (1, 2) . Although antibody responses to synthetic peptides are controlled by MHC genes in mice, experiments to show this in humans are less conclusive (3-5) and the presence or absence of response has not been associated with any specific HLA haplotype. Other studies in vitro using human cells have provided evidence for MHC immune suppression genes to collagen (6), cryptomeria japonica pollen (7), schistosomal antigen (Sj)t (8), and streptococcal cell wall 'Abbreviations used in this paper HB, hepatitis B ; HB&Ag, hepatitis B surface antigen; ML, ncobacterium leprae antigen ; NBCS, newborn calf serum; SCW, streptococcal cell wall antigen; Sj, schistosomal antigen .

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“…This phenomenon could also explain why occasionally IgG anti-HBs spots were undetectable in spite of the concurrent presence of anti-HBs in the serum. Several published observations support this concept [Stevens and Saxon, 1978;Callard et al, 1982;Cupps et al, 1984;Chang et al, 1984;Chiou et al, 1988;Filion et al, 19881. We and others have previously suggested the possibility of heterogenicity of the nonresponder which can be divided into groups of "pseudo-" and "real nonresponders," identified by their response following supplementary vaccination [Craven et al, 1986;Wismans et al, 19881. From the present data on the result of supplementary vaccination in hypo-and nonresponders we note that 13 out of 15 subjects with positive in vitro IgG anti-HBs spot formation did respond in vivo as well.…”

Section: Discussionmentioning

confidence: 90%

A prospective study of in vitro anti‐HBs producing B cells (spot‐ELISA) following primary and supplementary vaccination with a recombinant hepatitis B vaccine in insulin dependent diabetic patients and matched controls

Wismans¹,

Hattum²,

Gast³

et al. 1991

Journal of Medical Virology

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A prospective study of the immune response after hepatitis B vaccination was carried out in 32 insulin dependent diabetes mellitus (IDDM) patients and their age and sex matched healthy controls. A sensitive, immunoenzymatic technique was used, able to detect in vitro specific antibody production by mitogen stimulated individual B cells. In-vivo serologic response after vaccination with a standard scheme (0, 1 and 6 months) of 20 micrograms recombinant hepatitis B (HB) vaccine was significantly impaired in the IDDM patients both with respect to the number of nonresponders (25 versus 3%, P less than 0.05) and antibody titers reached (1,377 vs. 9,060 IU/L, P less than 0.05). The total number of in vitro IgM- and IgG-class immunoglobulin producing B cells as detected by the spot-ELISA, was found to be comparable in both groups. Specific IgG anti-HBs (and to a lesser extent IgM anti-HBs) showed impairment in the diabetic population as a whole. The number of IgG anti-HBs producing B cells was markedly depressed one month following vaccination, which is probably a reflection of homing of B cells outside the circulation. Responding subjects were identified early during their vaccination by the detection of in vitro anti-HBs production using the spot-ELISA. Non-responding healthy subjects and IDDM patients as a group showed a low number of IgG anti-HBs spots, suggesting a reduced specific memory B cell frequency. In 13 of 15 hypo- and nonresponders with positive IgG anti-HBs spots supplementary vaccination(s) resulted in improved anti-HBs levels.

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In vitro antigen-induced antibody responses to hepatitis B surface antigen in man. Kinetic and cellular requirements.

Abstract: Abstract. In

Cited by 27 publications

References 41 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

The cellular basis for lack of antibody response to hepatitis B vaccine in humans.

A prospective study of in vitro anti‐HBs producing B cells (spot‐ELISA) following primary and supplementary vaccination with a recombinant hepatitis B vaccine in insulin dependent diabetic patients and matched controls

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