In situ class switching and differentiation to IgA-producing cells in the gut lamina propria

One of the front lines of the immune defence is the gut mucosa, where immunoglobulin-alpha (IgA) is continuously produced to react with commensal bacteria and dietary antigens. It is generally accepted that, after antigenic stimulation in the Peyer's patches, IgA(+) lymphoblasts (B220(+)IgA(+)) migrate through the lymph and blood circulation, and eventually home to the lamina propria of the intestine(1,2). Mice that lack activation-induced cytidine deaminase (AID) are defective in class switch recombination (CSR) and somatic hypermutation(3). CSR changes the immunoglobulin heavy chain constant region (CH) gene being expressed from C mu to other CH genes, resulting in a switch of the immunoglobulin isotype from IgM to IgG, IgE or IgA. AID(-/-) mice also secrete large amounts of immunoglobulin-m (IgM) into faeces, and accumulate B220(-)IgM(+) plasma cells as well as B220(+)IgM(+) cells in the gut. Here we show that lamina propria B220(+)IgA(+) cells have just completed CSR, as they still express both AID and transcripts from circular DNA that has been 'looped-out' during CSR. Lamina propria IgM(+) B cells seem to be pre-committed to switching to IgA(+) in vitro as well as in vivo. Culturing lamina propria IgM(+) B cells together with lamina propria stromal cells enhances preferential switching and differentiation of B cells to IgA(+) plasma cells. We conclude that IgA(+) cells in the gut lamina propria are generated in situ from B220(+)IgM(+) lymphocytes.