Regulation of IgA expression by isotype-specific T cells and soluble binding factors.
The data presented here suggest a model for isotype-specific regulation of IgA synthesis by Fc alpha R+ T cells (Figure 1). Immature mIgM+ +/- mIgD+ B cells are induced by T switch cells to express cell surface IgA (a phenotypic switch). If the T switch cell induces mIgA expression via a long primary RNA transcript from an unrearranged C alpha allele, the hypothetical intermediate switch B cell results (step 1); this may be the mechanism of heavy chain expression in memory B cells that express low levels of Ig. Alternatively, T switch cells may induce a DNA rearrangement in the CH locus of the B cell (a genotypic switch), which results in a deletion of all CH loci except C alpha (step 2). TH inducer cells promote maturation of mIgA+ B cells to IgA-secreting plasma cells. This may involve a DNA switch rearrangement (step 3) or the maturation of previously switched cells (step 4), and appears to be mediated via an IgABF with enhancing activity. Not shown in this figure, but inherent in this model, is a suppressive regulatory arm that may be mediated via IgABF with suppressive activity released from Fc alpha R+ suppressor T cells. Due to the presence of Fc alpha R on a variety of cell types, IgABF may suppress synthesis of IgA by acting not only on mIgA+ B cells but also on regulatory cells (T cells, B cells, and macrophages) bearing IgA bound to Fc alpha R. If the IgA system is analogous with the IgE system, mIgA-bearing B cells may be the direct target of IgABF. Binding of Ig to FcR has been shown to (a) increase the number of Fc receptors per cell, (b) enhance the number of cells expressing Fc receptors, (c) induce the release of IgBF that either suppress or enhance Ig secretion, and (d) effectively convert surface Ig- cells into surface Ig+ cells that are therefore receptive to IgBF. Thus, FcR+ cells may interact with IgBF and Ig via a regulatory network to stimulate or inhibit the immune response in an isotype-specific manner. Cell surface molecules (mIg, FcR) may serve as sensors that allow the cell to detect and respond to fluctuations in the levels of immune mediators that serve to modulate Ig synthesis and secretion. The relationship between IgBF and FcR is not known, nor is it known whether Fc receptors expressed by different cell types are encoded by the same gene and are controlled similarly.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D000918:Antibody Specificity; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D007141:Immunoglobulin Fc Fragments; D011961:Receptors, Fc