Comment

In humans and most experimental mammals the gut lamina propria (LP) is the site of prodigious synthesis of the IgA isotype of immunoglobulin (Ig) and its secretion into the lumen. The major part of total Ig synthesis occurs here, leading to questions concerning the possible specific and non-specific stimuli of its production and the usefulness of this product to the host. Clearly, this typically continuous output of IgA is not constitutive as axenic (germ free (GF)) and newborn humans and other mammals display few secretory IgA plasmablasts in gut LP and minimal levels of secreted IgA in their gut lumen.1 ,2 In some way, colonisation with members of the normal gut microbiota seem to initiate the development and chronic activity of certain elements of the humoral mucosal immune system.3 ,4 This IgA consists of specific antibodies identifiably reactive with colonising bacteria, as well as of large quantities of IgA that cannot be shown to have been stimulated by or be reactive with particular antigens (Ags) present in food or microbes—so called “natural” IgA. In the mouse, the apparent duality of the IgA response might be explained by a difference in origin: firstly, conventional B cells (also called B2 cells) are specifically stimulated by microbial Ags and benefit from cognate interaction with Ag specific CD4⁺ T cells. They are clonally expanded in germinal centre reactions (GCR) in Peyer's patches (PP) and mesenteric lymph nodes, and benefit from the positive selection process occurring in GCR leading to affinity maturation that results in specific IgA antibodies.5 ,6 Secondly, a separate lineage of B cells, termed B1 cells, can be observed in the mouse. These cells, originally defined by expression of the surface marker CD5 and high expression of IgM, arise early in ontogeny, reside in the …