Antibody-dependent Cell-mediated Antibacterial Activity of Intestinal Lymphocytes with Secretory IgA

Secretory antibodies of the IgA class (sIgA) are thought to have an important role in the defence against bacteria at mucosal surfaces--the level at which the infectious agents first come into contact with the host. However, the mechanism by which sIgA exert their antibacterial activity is still a matter of debate. After the recent discovery of receptors for the Fc portion of IgA (RFc alpha) on lymphocytes, monocytes and granulocytes of human, rabbit, guinea pig and mouse origin, it has been hypothesized that IgA also mediate antibody-dependent cellular cytotoxicity (ADCC). Indeed, ADCC mediated by human leukocytes against bacteria has been demonstrated in the presence of human circulating IgA. As RFc alpha have also been shown to bind sIgA, we decided to investigate whether sIgA could mediate antibacterial ADCC when bound to lymphocytes from the murine gut-associated lymphoid tissues (GALT) which first interact with the invading bacteria. By using Shigella X16 (a hybrid strain between the enteric pathogen Shigella flexneri and Escherichia coli) as target in an in vitro assay that measures cell-mediated antibacterial responses, we found that murine lymphocytes from GALT but not from other tissues are able to exert natural antibacterial activity against Shigella X16, and that sIgA significantly and specifically increase the natural antibacterial activity of GALT lymphocytes from mice and induce antibacterial activity in cells from the spleen, but not from the thymus or popliteal lymph nodes. Thus, we now propose a new role for sIgA in protecting the host against infectious agents at the mucosal level.