The function of IgD

Notwithstanding a long series of experiments and hypotheses, the immunological function of IgD is still far from being completely understood. Many of these experiments were performed with heterologous or allogeneic anti-8 antibodies administered in vivo. The early ones were performed on monkeys using rabbit antihuman IgD antisera that cross-react with monkey IgD. The result was a marked polyclonal stimulation of immunoglobulin production, mostly of the IgG class, that included several antibodies to the different serum proteins of the heterologous anti-IgD antiserum. The mechanism of this marked reaction, that developed in a couple of weeks after the injection of the antiserum, was not clarified. With the isolation of murine IgD from a myeloma, and with the availability of purified hetero- or alloanti-mouse IgD antibodies, the study of the effect of administration of anti-IgD in vivo could make considerable progress.

Finkelman and coworkers have clearly shown that the polyclonal stimulation of B cells induced by heterologous anti-IgD, that eventually results in the production of IgGl, takes place in two stages, of which the first is T independent; the second involves T helper cells, activated by the heterologous immunoglobulins, that help the IgD+ cells to mature, switch to IgGl, and secrete the latter. The simplest interpretation is that B cells bind anti-IgD, process this foreign molecule, and present its fragments to T helper cells specific for it. However, this interpretation is not the only one. In fact, experiments with transferred congenic B cells of different allotype also point to the possibility that B cells activated by anti-IgD can use in a nonspecific fashion the large amount of cytokines produced by the activated T helper cells. This last possibility would be in agreement with the production of specific antibodies observed in the early experiments conducted with monkeys, that, as already noted, suggested an 'adjuvant' effect of the injection of heterologous anti-IgD antibodies.

It is clear, however, that protein ligands bound to membrane IgD can be processed very efficiently for presentation to T cells. Another possible interaction between IgD and T cells is through a receptor for IgD that is present on the membrane of a subpopul-ation of T cells; through this receptor IgD can stimulate T cells in a nonspecific fashion.

Double transgenic mice, which express both the gene for hen egg lysozyme (HEL) and the genes for a high-affinity anti-HEL antibody; are tolerant to HEL but contain high numbers of B cells with anti-HEL membrane Ig that is IgD and not IgM. Since tolerance to the antigen cannot be explained by suppressor T cells, it appears that this is somehow an intrinsic property of the IgD+ B cell population. IgD may therefore have a role in B cell tolerance. Curiously, such a role may favor tolerance, a view opposite to that entertained previously, when the observation that membrane IgD in murine B cells appeared after expression of IgM seemed to favor the interpretation that IgD could prevent B cell tolerance.

Interesting observations that shed some light on the function of membrane IgD have been made by Roes and Rajewsky in mice in which the 8 gene had been knocked out. In heterozygous mice the wild-type IgH locus was considerably overrepres-ented amongst the peripheral B cells and in particular in cells producing IgGl in response to a T-dependent antigen. In homozygous IgD-deficient mice affinity maturation of antibodies in a primary T cell-dependent response is delayed. This is again consistent with a role of the IgD receptors where the B cells are competing and are being selected for receptor affinity, such as in the germinal centers.

See also: B lymphocyte activation; B lymphocyte differentiation; Fc receptors; IgM; Immunoglobulin, cell surface; Immunoglobulin class switching; Immunoglobulin structure; Tolerance, peripheral.

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