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Intestinal IgA plasma cells of the B1 lineage are IL‐5 dependent

1998; Wiley; Volume: 94; Issue: 2 Linguagem: Inglês

10.1046/j.1365-2567.1998.00512.x

1365-2567

Shisan Bao, Kenneth W. Beagley, A. M. Murray, V. Caristo, Klaus I. Matthaei, Ian G. Young, A.J. Husband,

T-cell and B-cell Immunology

Two lineages of B cells, designated B1 and B2 cells, have been identified based upon their origins, anatomical distribution, cell surface markers, antibody repertoire and self‐replenishing potential. B1 cells are maintained by self‐renewal of cells resident in the peritoneal cavity (PerC) and they utilize a limited repertoire of germline V‐region genes, mostly directed against ubiquitous bacterial antigens such as phosphoryl choline (PC). B2 cells are replenished from bone marrow precursors and use a larger repertoire of immunoglobulin V‐region genes. Whereas most immunoglobulin A (IgA) plasma cells in the intestine derive from B2 lineage precursors in the Peyer’s patch, a subpopulation of Per C‐derived B1 cells populate the intestinal lamina propria where they mature into IgA plasma cells. In previous in vivo studies we have shown 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 have used IL‐5‐deficient mice to evaluate the role of IL‐5 in vivo in IgA 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 lineage 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 function but a defect in the B1 cell contribution to IgA responses in IL‐5 deficient mice. Collectively these data demonstrate differential cytokine 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. PerC, peritoneal cavity OVA, ovalbumin Ars, arsanilic acid HBBS, Hanks balanced salt solution LPL, lamina propria lymphocytes PE, phycoerythrin AOCC, anti‐OVA containing cells IPP, intra‐Peyer’s patch.