Microbe-dependent CD11b+ IgA+ plasma cells mediate robust early-phase intestinal IgA responses in mice

Abstract

Intestinal plasma cells predominantly produce immunoglobulin (Ig) A, however, their functional diversity remains poorly characterized. Here we show that murine intestinal IgA plasma cells can be newly classified into two populations on the basis of CD11b expression, which cannot be discriminated by currently known criteria such as general plasma cell markers, B cell origin and T cell dependence. CD11b+ IgA+ plasma cells require the lymphoid structure of Peyer’s patches, produce more IgA than CD11b− IgA+ plasma cells, proliferate vigorously, and require microbial stimulation and IL-10 for their development and maintenance. These features allow CD11b+ IgA+ plasma cells to mediate early-phase antigen-specific intestinal IgA responses induced by oral immunization with protein antigen. These findings reveal the functional diversity of IgA+ plasma cells in the murine intestine.

Re-thinking the functions of IgA+plasma cells

“…1 Our observations are in accordance with a recent report that describes a unique microbe-dependent subset of IgA C PC, mainly characterized as CD38 C CD138 C Blimp-1 C , which express CD11b and require IL-10 for their maintenance of IgA production. 102 These findings suggest that in the process of differentiating to become IgA C PC, the gut environment may have endowed IgA cells with 'monocytic' potential, a phenomenon that has been previously observed in.vitro 103 Moreover, B cells display non-conventional monocytic functions in other species 104 and in response to TLR ligation. 105 Previously, a subset of splenic B cells that regulate T cell function through their expression of indoleamine 2,3-dioxygenase was shown to express CD11c.…”

Regulation of Intestinal IgA Responses by Dietary Palmitic Acid and Its Metabolism

“…Mice received sodium bicarbonate to neutralize gastric acid before oral immunization (9,22). Thirty minutes later, the mice were immunized orally concurrently with 1 mg OVA (Sigma-Aldrich) and 10 mg cholera toxin (CT; List Biological Laboratories, Campbell, CA).…”

“…Cells were isolated from the intestinal lamina propria (iLP) as previously described (9,22). Briefly, PPs were removed, and small and large intestines were cut into 2-cm pieces, which were stirred in RPMI 1640 containing 1 mM EDTA and 2% FCS.…”

“…Detection of total Ig by ELISA and OVA-specific Ab responses by ELISPOT assay Total Ig levels in serum and fecal extracts were determined by ELISA, as previously described (9,22). To measure Ab concentration, purified murine isotype-specific Abs (BD Biosciences, San Jose, CA) were used as standards for quantification.…”

“…Indeed, germ-free mice have decreased intestinal IgA responses because of the immature structure of Peyer's patches (PPs) and isolated lymphoid follicles (7,8). We recently identified a unique subset of intestinal IgA-producing plasma cells (PCs) in the murine intestine; these cells expressed CD11b, required microbial stimulation and mature PP structure, proliferated vigorously, and produced high amounts of IgA (9).…”