Intestinal IgA plasma cells of the B1 lineage are IL-5 dependent.
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.
Bao
S
S
Department of Veterinary Anatomy and Pathology, University of Sydney, Australia.
Beagley
K W
KW
Murray
A M
AM
Caristo
V
V
Matthaei
K I
KI
Young
I G
IG
Husband
A J
AJ
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D018956:CD5 Antigens / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D007124:Immunoenzyme Techniques; D007070:Immunoglobulin A / Q000032:analysis* / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D015848:Interleukin-5 / Q000276:immunology*; D007422:Intestines / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D010767:Phosphorylcholine / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology*
D018956:CD5 Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015848:Interleukin-5; D010767:Phosphorylcholine; D010047:Ovalbumin