Simultaneous induction of specific immunoglobulin A–producing cells in major and minor salivary glands after tonsillar application of antigen in rabbits

Abstract

The immunoglobulin A (IgA)-producing cells in the stroma of major salivary glands are induced by antigenic stimulation of the mucosal immune system. Whether such cells also are induced in minor salivary glands by this stimulation remains to be determined. After application of sheep red blood cells to the palatine tonsils every 3 days for 6 weeks, anti-sheep red blood cell IgA was detected in saliva both by agglutination tests and by enzyme-linked immunosorbent assay. Using enzyme-linked immunospot assay, an increase in the number of anti-sheep red blood cell IgA-producing cells was found in minor as well as in major salivary glands of the sixth week of application; such cells constituted 4.9% to 5.9% of the total number of IgA-producing cells in these tissues. Tonsillar application of whole cells of formalin-killed Streptococcus sobrinus induced anti-S. sobrinus IgA in saliva. The number of anti-S. sobrinus IgA-producing cells in the above glands simultaneously increased over 6 weeks, and reached 5.2-5.6% of the total number of IgA-producing cells.

Characteristics of Human IgA and IgM Genes Used by Plasma Cells in the Salivary Gland Resemble Those Used in Duodenum But Not Those Used in the Spleen

“…This observation is consistent with the salivary gland being part of the common mucosal immune system, which is separate from the peripheral immune system. It has been shown that in rabbits the tonsil can be an inductive site producing the effector cells of the salivary gland (5). Previously published data on the number of mutations in genes from human tonsil (16) has shown that there are some highly mutated IgA V H genes in tonsil, but the overall frequency of mutation of IgA V H genes in tonsil is still significantly less than that seen for the salivary gland IgA V H genes.…”

“…It has been suggested that the palatine and nasopharyngeal tonsils may be the inductive sites, because they may be the equivalent of the rodent nasal-associated lymphoid tissue (3), which is the inductive site for salivary glands in mice (4). It has also been shown that direct immunization of palatine tonsils in the rabbit results in specific IgA Ab-producing cells in the salivary gland (5). Nasopharyngeal IgA Ab levels have been shown to be decreased after tonsillectomy and adenoidectomy of young children (6).…”

Streptococcus sobrinus Antigens That React to Salivary Antibodies Induced by Tonsillar Application of Formalin-Killed S. sobrinus in Rabbits

“…We do not know why tonsillar application and intramuscular injection of the same S. sobrinus organisms resulted in differences in recognizing antigens. By both routes, IgG was the predominant antibody in blood plasma, and many specific IgG-producing cells, probably the source of the blood plasma IgG, were detected in the spleen (13). There must be differences in the steps from antigen incorporation to antibody production in the spleen.…”

“…Tonsillar application of sheep erythrocytes (4) and formalin-killed bacterial cells (7,13) induced production of salivary immunoglobulin A (IgA) and blood plasma IgG more effectively than did intragastric instillation or nasal application. In rabbits immunized by tonsillar application of formalin-killed Streptococcus sobrinus, a cariogenic bacterium, the experimental dental caries were suppressed to one-fifth of the level found in nonimmunized rabbits and to one-third of the level in rabbits immunized by the intragastric route (7).…”

“…Over the past several years, we have been developing tonsillar application, a new immunization route for mucosal immunity, specifically for the oral cavity (3)(4)(5)(6)(7)13). Tonsillar application of sheep erythrocytes (4) and formalin-killed bacterial cells (7,13) induced production of salivary immunoglobulin A (IgA) and blood plasma IgG more effectively than did intragastric instillation or nasal application.…”