About this Research Topic
Despite its central role, IgA antibody formation in the gut immune system is still incompletely understood. In humans, several grams of IgA are produced each day, and this together with mucins and other soluble components constitutes the first line of defense of the gut mucosal barrier. Plasma cells, at the effector site in the mucosal membrane, form IgA dimers, which are actively transported through the epithelium into the gut lumen as secretory IgA. New IgA plasma cells are constantly generated in the gut through class switch recombination (CSR) of antigen-activated naïve IgM B cells, a process that has been found to greatly depend on gut microbiota. Most IgA CSR in the gut occurs in the gut associated lymphoid tissues (GALT), which consist of Peyer’s patches (PP), intestinal lymphoid follicles (ILF) and mesenteric lymph nodes (MLN). In addition, colon patches, apart from ILFs, have been ascribed an inductive role for mucosal IgA responses following intra-rectal immunizations. An alternative, but quite controversial, site for IgA CSR is the non-organized lamina propria (LP) of primarily the large intestine. Evidence in support of IgA CSR in the LP is still scarce and several investigators have recently failed to confirm earlier observations.
Two main developmental pathways have been described for the generation of IgA plasma cells in the gut LP; a T-cell dependent (TD) and a T-cell independent (TI) pathway. Much interest has focused on the development of IgA antibodies against the microflora of the gut. To what extent the small and large intestine reflect the same or different IgA responses has been poorly studied. Considering that the microbiota is hosted mainly in the large intestine, it is surprising that IgA plasma cells are more abundant in the small intestinal LP. Furthermore, strong oral immunogens like cholera toxin are well known to stimulate not only gut mucosal IgA , but also very substantial serum IgG responses. To what extent these responses emanate from the same inductive sites or not, has been poorly investigated.
This Research Topic aims at bringing together recent research that can shed light on some basic principles of how IgA B cell responses are induced and regulated. In particular, we hope to achieve a better concensus as to the role of different inductive sites that have been proposed to be involved in gut IgA B cell responses against the gut microbiota (TI) as opposed to those that are engaged in responding to food antigens and vaccines (TD). Are they the same or different? Does IgA class switch recombination and somatic hypermutation in the GALT require germinal centers and can these be shared by B cells activated by bacteria as well as food or vaccine antigens?
Two main developmental pathways have been described for the generation of IgA plasma cells in the gut LP; a T-cell dependent (TD) and a T-cell independent (TI) pathway. Much interest has focused on the development of IgA antibodies against the microflora of the gut. To what extent the small and large intestine reflect the same or different IgA responses has been poorly studied. Considering that the microbiota is hosted mainly in the large intestine, it is surprising that IgA plasma cells are more abundant in the small intestinal LP. Furthermore, strong oral immunogens like cholera toxin are well known to stimulate not only gut mucosal IgA , but also very substantial serum IgG responses. To what extent these responses emanate from the same inductive sites or not, has been poorly investigated.
This Research Topic aims at bringing together recent research that can shed light on some basic principles of how IgA B cell responses are induced and regulated. In particular, we hope to achieve a better concensus as to the role of different inductive sites that have been proposed to be involved in gut IgA B cell responses against the gut microbiota (TI) as opposed to those that are engaged in responding to food antigens and vaccines (TD). Are they the same or different? Does IgA class switch recombination and somatic hypermutation in the GALT require germinal centers and can these be shared by B cells activated by bacteria as well as food or vaccine antigens?
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