The ocular humoral immune response in health and disease

This review focuses on several aspects of humoral immunologic defence of the ocular surface and intraocular compartment. Secretory IgA (sIgA) is a major component of lacrimal fluid and contributes to the first line of defence against infection of the ocular surface. Recent findings show that part of the lacrimal gland (LG) IgA repertoire consists of so-called natural IgA antibodies. How B cells responsible for these natural IgA antibodies are distributed to effector mucosal sites like the LG is not known. Extensive data are now available on the regionalization of mucosal IgA responses in murine gut, involving peritoneal B cells, the prototypic natural antibody producing cells. By comparing elaborate experiments done in mice with the much less extensive data on the LG, it becomes clear that this gland is a unique, but poorly investigated effector organ of the mucosal immune system. In addition to the humoral immune response at the surface of the eye, the production of antibodies within the ocular compartment also has several fascinating features. The detection of pathogen-specific antibodies in intraocular fluid (IOF) of uveitis patients is accepted as a diagnostic tool, but the specificity of these intraocular antibodies was not investigated in much detail. Recent data however, demonstrate that even antibodies recognizing the same antigen in both serum and IOF still differ in the epitopes they recognize. This reveals that the intraocular compartment largely determines its own antibody profile in the defence against intra-ocular pathogens. Several models as to how an exclusive intra-ocular B cell repertoire may be generated are presented.