EVIDENCE FOR IDENTITY OR CLOSE ASSOCIATION OF THE Fc RECEPTOR OF B LYMPHOCYTES AND ALLOANTIGENS DETERMINED BY THE <i>Ir</i> REGION OF THE <i>H-2</i> COMPLEX

The ready availability of inbred strains, ability to withstand microvascular surgery, and the ease of production of immunological enhancement have made the rat a popular and valuable model for organ transplantation. A number of studies in the mouse employing skin allografts have demonstrated the central role of gene products of the major histocompatibility H-2 complex in the rejection process. Fragmentary understanding of the rat major histocompatibility gene complex (MHC) 1 has limited the general applicability of data obtained by studying rat organ transplantation. Because important differences exist between the immunobiology of skin and organ allografts (1), it is important to develop a full understanding of the rat MHC. Recent studies have indicated that rat gene products identical to or closely linked to the serologically defined Ag-B system function as immune response genes (2, 3) and stimulate the mixed lymphocyte culture response (4). These studies suggest, therefore, that the rat MHC bears close similarity to the more extensively mapped MHC regions of primates and the mouse.The phenomenon of passive enhancement of tumor and tissue allografts (1, 5) has been shown to be associated with only minimal alteration in cellular immune responsiveness in the host (6). In contrast, immunopathological (7,8) and humoral studies (6-9) have emphasized the depression of host humoral responsiveness and suggest an impairment of B-T-cell cooperation (6). Still, the mechanism by which passive immunization produces this deviation in the immune response remains speculative. An important recent advance has been the finding that, while antibodies of different classes (10) and physicochemical characteristics (11) can induce enhanced graft survival, antibodies specific for the products of the K and D regions of the mouse MHC are unnecessary (12). Similarly, in the rat,

Section: Discussioncontrasting

confidence: 55%

“…Rabbit antirat IgG inhibited EA rosette formation, but this effect was not strain specific. Blocking of FITC-IgG aggregate binding (16) was also produced by HIS and PAS. SAS was devoid of any blocking activity.…”

Section: In Vitro Studiesmentioning

confidence: 99%

The role of nonclassical Fc receptor-associated, Ag-B antigens (Ia) in rat allograft enhancement.

Soulillou¹,

Carpenter²,

d’Apice³

et al. 1976

“…The previous experiment indicated that H-2-associated antigens were not in close proximity to the region of the antigen-binding (Ig) determinants on B cells . The question therefore arose whether other sites, such as the Fc receptors, were more closely linked to H-2 determinants since a role for the Fc receptor had been postulated in the regulation of B-cell activity (3,7). Spleen cells from CBA/H/WEHI (H-2k) mice were incubated with anti-H-2 serum directed against H-2k or H-2b determinants, washed, and then labeled with anti-FyG "5I-labeled FyG in the standard manner.…”

Section: Effect Of Pretreatment Withmentioning

confidence: 99%

Relationship between Fc receptors, antigen-binding sites on T and B cells, and H-2 complex-associated determinants.

Basten¹,

Miller²,

Abraham³

1975

The relationship between H-2 complex-associated determinants, Fc receptors, and specific antigen-recognition sites on T and B cells was examined by binding and functional assays. The Fc receptor was detected by radiolabeled immune complexes or aggregated human IgG. Both these reagents selectively bound to B cells, not to T cells. When spleen cells, from mice primed to several antigens, were exposed to highly substituted radioactive aggregates, their capacity to transfer both a direct and indirect plaque-forming cell response to these antigens was abrogated. Addition of B cells, but not of T cells, restored responsiveness. Complexed Ig binding to Fc receptors was prevented by pretreatment of mixed lymphoid cell populations with antisera directed against membrane components on the same cell (e.g., H-2) and on other cells (e.g., theta). The lack of specificity of inhibition was thought to be due to the formation on cell surfaces of antigen-antibody complexes which would then attach to the Fc receptor during the incubation precedure. Specific blockade of the Fc receptor during the incubation procedure. Specific blockade of the Fc receptor however occurred when B cells were pretreated with the Fab fragments of anti-H-2 antibody. This was demonstrated autoradiographically and by inhibition of aggregate-induced suicide. The blocking activity of ante-H-2 Fab was removed by absorption with spleen cells from thymectomized irradiated mice but not with thymus cells of appropriate specificity. This suggested that the antibodies involved had specificity for determinants on the B-cell membrane distinct from those coded by the K or D end of the H-2 complex, and either absent from, or poorly represented on, thymus cells. Specific antigen-induced suicide of B cells was achieved simply by incubating the cells with radioactive antigen in the cold. T-cell suicide on the other hand required that the 125I-labeled antigen be presented to the T cells at 37 degrees-C on the surface of spleen cells from antigen-primed mice. Pretreatment of T cells with the Fab fragment of anti-H-2 antibody protected them from the suicide effect. By contrast no such protection of B cells could be achieved by this procedure. In other words H-2 (? Ir)-associated determinants may not only be in close proximity to the antigen-binding site on T cells but, in addition, may be involved in the effective operation of the receptor.

“…In the first method, specific ligand (usually antibody) is bound to molecule A and the ability to serologically detect molecule B is subsequently evaluated. Using this method, interactions have been reported between Ia antigens and Fc IgG receptors (FcGR) 1 (1,2) and LyM antigens and FcGR (3) on B lymphocytes, and between Ia antigens and FcGR (4,5), H-2D b and Lyt 2.2 (6, 7), H-2K b and Lyt 1.2 (6, 7), H-Y and TL (8), D b and TL (6,7), and H-Y and D b (8) on T lymphocytes. The simplest (but not the only) interpretation of these data is that the interacting molecules are specifically (nonrandomly) located in close proximity to each other on the lymphocyte surface membrane.…”

mentioning

confidence: 99%

Interactions between lymphocyte membrane molecules. I. Interaction between B lymphocyte surface IgM and Fc IgG receptors requires ligand occupancy of both receptors.

Dickler¹,

Kubicek²

1981

The independent B lymphocyte surface membrane receptors IgM and Fc IgG receptors were evaluated for interactions using immunoflourescence. Ligand [F(ab')2 anti-mu]-induced capping of surface IgM resulted in capping of Fc IgG receptors only if the latter were occupied during the capping process by: (a) soluble antigen-antibody complexes that themselves provided insufficient cross-linking to result in capping; or (b) monomeric IgG at physiologic concentrations (or less) either purified or as normal serum. Ligand-induced capping of Fc IgG receptors did not result in capping of surface IgM occupied by monomeric F(ab') anti-mu. Control experiments showed that ligand binding to or capping of only one of these two receptors has no effect on the other, and that there were no cross-reactions. The interaction appears specific in that ligand-induced capping of surface IgM did not induce capping of ligand-occupied surface IgD or I-A antigens. Thus, there appears to be a specific interaction between ligand-bound surface IgM and ligand-bound Fc IgG receptors on the B lymphocyte surface. The results also indicate that binding of monomeric IgG produces a reversible alteration in the Fc IgG receptor leading to association with ligand-bound surface IgM. Because Fc IgG receptors are continuously exposed to monomeric IgG in vivo, these results suggest that whenever surface IgM is involved in a B lymphocyte response to an immunologic stimulus, the Fc IgG receptor is also involved.