Could the airway epithelium play an important role in mucosal immunoglobulin A production?

Immunoglobulin (Ig) A is the major immunoglobulin of the healthy respirator y tract and is thought to be the most important immunoglobulin for lung def ence. The basis for the preferential generation of IgA-secreting cells in t he airway mucosa remains unclear. Given the half-life of 5 days for the maj ority of IgA plasma cells, many IgA plasma cells must develop daily from B cells to guarantee a continuous supply of IgA antibodies in the airway muco sa. For this, the surrounding cells must provide a constant supply of cytok ines necessary for B-cell isotype switch, growth and differentiation into I gA-secreting plasma cells. Studies with CD4(+) T-cell knockout mice, T-cell receptor knockout mice and mice made transgenic for CTLA4-Ig demonstrate n ormal mucosal IgA isotype switch, differentiation and IgA production, there by suggesting that T cells are not critical for mucosal IgA production, and that other cell sources may be more important. Also, the bronchus-associat ed lymphoid tissue (BALT), which is believed to be the major site where IgA isotype switch and differentiation of B cells into plasma cells occur with the help of cytokines released by T cells, is not a constitutive feature o f the normal human lung. This indicates that other parts of the respiratory tract must carry out the BALT function. We have recently demonstrated that healthy human airway epithelial cells constitutively produce IL-5, a major cytokine implicated in the growth and differentiation of post-switch mIgA( +) B cells to IgA-producing plasma cells. Several studies have recently rep orted that the human airway epithelium also constitutively produces IL-2, T GF beta, IL-6 and IL-10, factors which are essential for B-cell clonal prol iferation, IgA isotype switch and differentiation into IgA-producing plasma cells. The close proximity of B cells to the airway epithelium probably en sures a constant supply of growth and differentiation factors necessary for mucosal IgA production. In addition, the epithelial cells produce a glycop rotein, called the secretory component, which not only confers increased st ability to S-IgA, but is also quantitatively the most important receptor of the mucosal immune system, since it is responsible for the external transp ort of locally produced polymeric IgA and IgM. Recent studies also suggest a possible role for epithelial cells in antigen presentation. Dendritic cel ls situated within the airway epithelium could directly present antigens to B cells and direct their isotype switch towards IgA(1) and IgA(2) with the help of cytokines produced by epithelial cells. Airway epithelial cells co uld therefore play a major role in the production of mucosal IgA antibodies which are essential for airway mucosal defence.