B cells on the podium: regulatory roles of surface and secreted immunoglobulins

Manca, Fabrizio; Fenoglio, Daniela; Kunkl, Annalisa; Cambiaggi, Caterina; Pira, Giuseppina Li; Celada, Franco

doi:10.1016/0167-5699(88)91321-7

Cited by 30 publications

(16 citation statements)

References 23 publications

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“…We have shown that p66-specific Tcells can recognize HIV internalized by APC in complexed form with gp41 or with gp120 mAb. Ab-mediated Ag uptake, involving FcR on APC [40-421, mimicks antibody-dependent antigen uptake by B cells [41].Therefore, it is logical to design helper assays with humanTh and B cells specific for p66 and gp120, respectively.…”

Section: Discussionmentioning

confidence: 99%

Human T helper cells specific for HIV reverse transcriptase: possible role in intrastructural help for HIV envelope‐specific antibodies

et al. 1995

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Cooperation between B cells specific for an antigen exposed on a viral structure and T helper (Th) cells specific for an internal antigen, as demonstrated with influenza, hepatitis B and rabies viruses, has been termed intrastructural help. Th cells specific for internal proteins of HIV, which are much less mutated than its exposed antigens, may be valuable in vaccine design against this virus. We investigated the human Th repertoire specific for the core HIV antigen reverse transcriptase (p66), and determined whether these cells could be candidate intrastructural T helpers. CD4+ T lines and clones were generated from non-immune individuals by stimulation with p66-pulsed antigen-presenting cells (APC). Specific lines were obtained with p66 from 19 out of 21 (90%) of these individuals, vs. 7 out of 29 (24%) with gp120. Diverse epitopes were recognized by different individuals, and various V beta genes were used by these clones. Clones using the same V beta genes were of diverse origin, according to VDJ region sequence. Of these lines 45% responded to p66 in the context of HIV virions. Moreover, p66-specific clones could respond to APC that had internalized HIV complexed with envelope-specific monoclonal antibodies, suggesting that p66-specific Th cells may participate in intrastructural help. These studies indicate that p66-specific Th cells are detectable in vitro in most naive individuals and exhibit clonal heterogeneity, and that the majority recognize an HIV conserved antigen. They respond to p66 following processing of whole virions and are clearly candidates for intrastructural help. If confirmed in vivo, p66 should be included among vaccine candidates investigated to optimize the anti-HIV Th response.

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Section: Discussionmentioning

confidence: 99%

Human T helper cells specific for HIV reverse transcriptase: possible role in intrastructural help for HIV envelope‐specific antibodies

et al. 1995

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“…Alternatively, spreading of autoimmunity could follow from enhanced Fc receptor-mediated uptake and antigen presentation of La/Ro RNP immune complexes by professional antigen-presenting cells (47)(48)(49)(50) The findings presented here suggest how an autoimmune response to a single region of a self-antigen could trigger intraand intermolecular autoimmune spreading to involve associated self-components. Indeed, initiation of immunity might also involve a response to foreign antigens linked to selfcomponents as has been described (8,51).…”

Section: Discussionmentioning

confidence: 99%

Intra- and intermolecular spreading of autoimmunity involving the nuclear self-antigens La (SS-B) and Ro (SS-A).

Topfer

Gordon

McCluskey

1995

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

176

132

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We have tested the extent of immune selftolerance to the ubiquitously expressed nuclear/cytoplasmic (5), and contains species-specific epitopes (6). These studies are consistent with molecular mimicry (7) or "altered self' (8) acting as an initiating event ultimately leading to antigen-driven autoimmunity. However, it is unclear how these mechanisms could lead to simultaneous targeting of the La and Ro autoantigens in Sjogren syndrome (2) or result in the specific subsets of anti-nuclear antibodies associated with other autoimmune disorders (1). La is an ATP-dependent (9) transcription-termination factor for RNA polymerase III (10) that binds the 3' uridine-rich region of polymerase III RNA transcripts (11). At least two Ro polypeptides have been identified: 52-kDa Ro and 60-kDa Ro (Ro60). The function of the Ro proteins is undefined; however, it is known that Ro6O associates with the Y RNAs (cytoplasmic small RNAs) (12) and, at least transiently, with the La molecule (13,14). Thus it is possible that the occurrence of autoantibodies to both La and Ro in autoimmune disease is a consequence of their structural association intracellularly (2).We have examined whether immunity to La and Ro6O autoantigens can be triggered by immunization with recombinant antigen in normal, healthy mice. The data indicate incomplete immune tolerance to the La and Ro autoantigens after immunization of normal mice and show that initiation of immunity to a single component of the La/Ro RNP complex is sufficient to trigger autoantibodies reactive with other components of this complex.

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“…Furthermore, complexing an antigen with specific antibody modulates antigen uptake, processing and presentation by APC [8]. We have shown previously that IC influence the balance between Thl and Th2 cytokines [9, 101.…”

Section: Introductionmentioning

confidence: 99%

Immune complexes are potent inhibitors of interleukin‐12 secretion by human monocytes

et al. 1997

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We have studied the effect of immune complexes (IC) on interleukin (IL)-12 secretion by human monocytes in vitro. Two experimental models of IC were used. IC formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum IgG almost completely inhibited IL-12 (p70 and p40) secretion induced by interferon-gamma and lipopolysaccharide in human blood-derived monocytes. Neutralizing anti-IL-10 antibodies plus indomethacin restored IL-12 secretion in the presence of IC to a high extent, indicating that IL-10 and prostaglandin (PG) partially mediate the IC-induced inhibition of IL-12 secretion. However, neutralization of tumor necrosis factor (TNF)-alpha by specific antibodies also incompletely restored IL-12 secretion. Indeed, monocytes secrete high levels of TNF-alpha upon stimulation by IC. We found that exogenously added TNF-alpha caused a profound inhibition of monocytic IL-12 secretion in the absence of IC, again mediated via the induction of IL-10 and PG. In summary, IC inhibit IL-12 secretion via TNF-alpha-induced IL-10 and PG synthesis. We conclude that IC, typically appearing in the course of chronic inflammatory processes, may influence the balance between Th1 and Th2 responses and may thus contribute to a deprivation of cell-mediated immune responses.

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B cells on the podium: regulatory roles of surface and secreted immunoglobulins

Cited by 30 publications

References 23 publications

Human T helper cells specific for HIV reverse transcriptase: possible role in intrastructural help for HIV envelope‐specific antibodies

Human T helper cells specific for HIV reverse transcriptase: possible role in intrastructural help for HIV envelope‐specific antibodies

Intra- and intermolecular spreading of autoimmunity involving the nuclear self-antigens La (SS-B) and Ro (SS-A).

Immune complexes are potent inhibitors of interleukin‐12 secretion by human monocytes

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