INTESTINAL IGA PLASMA-CELLS OF THE B1 LINEAGE ARE IL-5 DEPENDENT

Two lineages of B cells, designated B1 and B2 cells, have been identif ied based upon their origins, anatomical distribution, cell surface ma rkers, antibody repertoire and self-replenishing potential. B1 cells a re maintained by self-renewal of cells resident in the peritoneal cavi ty (PerC) and they utilize a limited repertoire of germline V-region g enes, mostly directed against ubiquitous bacterial antigens such as ph osphoryl choline (PC). B2 cells are replenished from bone marrow precu rsors and use a larger repertoire of immunoglobulin V-region genes. Wh ereas most immunoglobulin A (IgA) plasma cells in the intestine derive from B2 lineage precursors in the Peyer's patch, a subpopulation of P er C-derived B1 cells populate the intestinal lamina propria where the y mature into IgA plasma cells. In previous in vivo studies we have sh own that whereas IgA(+) B2 cells are interleukin (IL)-6 dependent, B1 cells are IL-6 independent. In view of the in vitro evidence that IL-5 is also involved in IgA expression, in the studies reported here we h ave used IL-5-deficient mice to evaluate the role of IL-5 in vivo in I gA expression in the gut. The results demonstrate that although total IgA cell numbers are only marginally depressed in IL-5-deficient mice, there is a marked selective depletion of IgA(+) cells of the B1 linea ge in the gut and a corresponding depression in the capacity of these mice to mount an intestinal response to a B1 antigen (PC) but not to a B2 antigen (oralbumin; OVA), reflecting intact B2-derived IgA cell fu nction but a defect in the B1 cell contribution to IgA responses in IL -5 deficient mice. Collectively these data demonstrate differential cy tokine regulation of subsets of IgA(+) cells in the gut in that IgA(+) cells of the B2 lineage are IL-6 dependent but IL-5 independent, but B1-derived IgA(+) cells are IL-5 dependent and IL-6 independent.