Role of the Fc Fragment in the Regulation of the Primary Immune Response

Sinclair, Nicholas; Lees, Rosemary K.; Elliott, E. V.

doi:10.1038/2201048a0

Cited by 41 publications

(36 citation statements)

References 11 publications

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“…This was accomplished by removing the Fc portion, and the resulting F(ab02 antibody was tested for its ability to inhibit immunological priming (the establishment of immunological memory). Previous results from this laboratory indicated that F(ab02 antibody was much less effective than whole antibody in inhibiting the primary hemolysin response to sheep erythrocytes (12), and the experiments reported here indicate…”

supporting

confidence: 60%

Regulation of the Immune Response

Sinclair

1969

The Journal of Experimental Medicine

168

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The ability of 7S and F(ab')2 antibody fragments to suppress priming with low doses of antigen was compared. The 7S preparation was approximately 100–1000 times more potent than the F(ab')2 preparation when the agglutinin titers of the two preparations were the same. The presence of any ability to suppress priming in the F(ab')2 preparation may reflect an inherent capacity of the F(ab')2 antibody or contamination with small amounts of 7S antibody. The difference between 7S and F(ab')2 antibody in ability to suppress priming is attributed to the lack of the Fc portion on the F(ab')2 antibody. The Fc portion may be needed to prevent rapid excretion of antibody from the body, to induce rapid phagocytosis of antigen-antibody complexes with consequent breakdown and elimination of antigen, or to inactivate or suppress the antigen-sensitive cells from reacting to antigenic determinants. More detailed studies will permit a better assessment of the importance of these three possible regulatory roles of the Fc portion of the immunoglobulin in the immune response.

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supporting

confidence: 60%

Regulation of the Immune Response

Sinclair

1969

The Journal of Experimental Medicine

168

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“…The Fc dependence of anti-erythrocyte-mediated AMIS effects has been suggested from the finding that the inhibition can be nonepitope specific, where Abs to one Ag can inhibit the response to another Ag on the same erythrocyte (14, 17, 48-51), as well as from several studies demostrating that F(ab9) 2 fragments could be poor suppressors (17,48,52,53). A study by Karlsson and colleagues (16) using haptenated SRBC showed that anti-hapten mAbs suppress the Ab response in mice lacking the FcgRIIB as well as activating FcgRs or the neonatal Fc receptor (FcRn).…”

Section: Discussionmentioning

confidence: 99%

IgG-Mediated Immune Suppression to Erythrocytes by Polyclonal Antibodies Can Occur in the Absence of Activating or Inhibitory Fcγ Receptors in a Full Mouse Model

Bernardo

Amash

et al. 2015

The Journal of Immunology

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Polyclonal anti-D has been used to prevent RhD-negative mothers from becoming immunized against RhD positive fetal erythrocytes, and this mechanism has been referred as Ab or IgG-mediated immune suppression (AMIS). Although anti-D has been highly successful, the inhibitory mechanisms remain poorly understood. Two major theories behind AMIS involve the binding of IgG to activating or inhibitory FcγR, which can induce either erythrocyte clearance or immune inhibition, respectively. In this work, we explored the absolute role of activating and inhibitory FcγR in the AMIS mechanism using the HOD mouse model of RBC immunization. HOD mice contain a RBC-specific recombinant protein composed of hen egg lysozyme (HEL), OVA and human transmembrane Duffy Ag, and erythrocytes from HOD mice can stimulate an immune response to HEL. To assess the contribution of activating and inhibitory FcγR to AMIS, C57BL/6 versus FcRγ-chain−/− or FcγRIIB−/− mice were used as recipients of HOD-RBC alone or together with anti-HEL Abs (i.e., AMIS) and the resulting immune response to HEL evaluated. We show that anti-HEL polyclonal Abs induce the same degree of AMIS effect in mice lacking these IgG binding receptors as compared with wild-type mice. In agreement with this, F(ab′)2 fragments of the AMIS Ab also significantly reduced the Ab response to the HOD cells. In conclusion, successful inhibition of in vivo Ab responses to HOD-RBC by polyclonal IgG can occur independently of activating or inhibitory FcγR involvement. These results may have implications for the understanding of RhD prophylaxis.

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“…USA 96 (1999)in vitro are memory cells derived from spleens primed with high doses of antigen in vivo. In addition to in vitro studies, the view that IgG-mediated suppression is Fc-dependent was suggested by two types of experimental in vivo findings, both of which are controversial: the inability of F(abЈ) 2 fragments to induce suppression (4,8,17,18) and the ability of IgG to induce non-epitope-specific suppression (3,8,18,23). There are many difficulties in working with F(abЈ) 2 fragments, and, in retrospect, it is hard to explain the reason for the conflicting results discussed earlier.…”

Section: Discussionmentioning

confidence: 99%

“…The most straightforward way of analyzing this is to compare the suppressive ability of intact IgG with that of F(abЈ) 2 fragments (where the Fc part has been proteolytically cleaved off). Such studies performed in vivo have given discrepant results, some claiming that F(abЈ) 2 fragments are less suppressive (4,8,17,18) and others claiming that they are equally suppressive as intact IgG (19,20). An indirect way of assessing Fc dependence has been to study whether or not suppression is epitope-specific.…”

mentioning

confidence: 90%