Natural polyreactive secretory immunoglobulin A autoantibodies as a possible barrier to infection in humans

Abstract

Secretory immunoglobulin A (S-IgA) was investigated in human secretions for the presence of natural antibodies (Abs) acting as the first "immune barrier" to infection before induction or boosting of specific responses. These molecules could be the secretory counterpart of the natural Abs in serum that were previously shown by our laboratory to be polyreactive to autoantigens. Significant levels of S-IgA Abs to human actin, myosin, tubulin, and spectrin were detected in 10 saliva and 8 colostrum samples from normal subjects. Computer-assisted analysis of immunoblots of extracts from human muscles showed these Abs to react with a large number of autoantigens. Their polyreactivity was confirmed by cross-inhibition and by immunoblotting studies of affinity-purified natural Abs, assayed against a large variety of surface or secreted antigens from Streptococcus pyogenes. The thiocyanate elution method showed that functional affinities of some natural Abs can be of the same order of magnitude as those of tetanus vaccine antitoxins. Moreover, nonimmune binding of these natural Abs to the gut protein Fv (Fv-fragment binding protein) can enhance their effector functions. This demonstrates that human secretions contain polyreactive auto-Abs which can also react with pathogens. These secretory Abs of "skeleton key" specificities are possibly produced by a primordial B-1-cell-associated immune system and can be involved in a plurispecific mucosal protection against pathogens, irrespective of the conventional immune response.

Innate secretory antibodies protect against natural Salmonella typhimurium infection

“…In contrast to fi ndings by Bouvet et al (19,24), preabsorbtion of pIgR −/− serum with S. typhimurium only removed a small fraction of the total IgA and did not reduce the bind-ing to other commensals. SIgA forms large multivalent complexes with mucins and/or pFv after secretion (26), which may aff ect the quantitative analysis of binding of SIgA to antigens.…”

Enhanced differentiation of intraepithelial lymphocytes in the intestine of polymeric immunoglobulin receptor‐deficient mice

“…These results confirm that serum IgA in pIgR À/À mice has properties similar to natural polyreactive sIgA. 18 Therefore, we consider that pIgR À/À mice can be used to reveal the abnormalities caused by the lack of secretory antibody.…”

Mucosal Immunoglobulins

“…It has been proposed that S-IgA comprises high levels of naturally occuring antibodies that provide an effective barrier to infection, due to their polyreactivity with seemingly unrelated antigens (176). Such polyreactive antibodies are generated by somatic mutations, particularly in the third CDR of the a chain variable region; in turn, these changes substantially alter the specificity of IgA antibodies (177)(178)(179).…”