Regulation of secretory immunity

The biological significance of the striking J chain expression shown by Ig-producing cells in exocrine tissues is that plgA and plgM are generated locally and thus become readily available for plgR-mediated external transport. This important goal, in terms of clonal B cell differentiation, may be sufficient justification for the J chain to be expressed also by a variable fraction of B cells terminating in exocrine tissues with IgD or IgG production; these immunocytes may be considered as 'spin-offs' from recently stimulated memory B cells that through clonal isotype switching are on their way to IgA expression. The J chain appears to be a marker of fairly recently differentiated B cell memory clones, and no other function has been identified for this peptide than incorporation into the quaternary structure of plgA and plgM, thereby contributing to their SC plgR binding site (see above). This incorporation takes place intracellular^ as shown by the preferential binding of free SC to the cytoplasm of mucosal IgA and Ig.Vl immunocytes in affinity tests performed on tissue sections (color plate).

The precursors for Ig-producing cells in exocrine tissues are apparently in the main derived via lymph and peripheral blood from organized Ivmphoepithel-ial structures where the primary mucosal B cell responses are induced. The most important inductive site seems to be the gut-associated lymphoid tissue (GALT), particularly the Peyer's patches; but bronchus-associated lymphoid tissue (BALT) and probably the tonsils also contribute, especially to plasma cell populations in the upper alimentary and respiratory tracts.

It has been known for more than two decades that Peyer's patches are enriched in IgA-producing cell precursors. Some immunoregulatory mechanism) s) must exist in GALT and similar mucosa-associated lymphoid tissue (MALT) that facilitates expansion of early memory clones with activated J chain gene while allowing very little terminal B cell differentiation in situ. The final maturation to pig-producing plasma cells will therefore mainly take place after precursor distribution to exocrine effector sites. Although uptake of antigens by lymphoepithelial MALT structures, and the involvement of antigen-presenting cells, T cells and various cytokines have been subjected to extensive studies, it remains obscure how B cells of the mucosal immune system normally are tuned for activation of the J chain gene and preferential plgA responses.

Studies in our laboratory as well as by other groups have shown that SC/pIgR expression by secretory epithelium may be modulated by cytokines

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