IL-9-induced expansion of B-1b cells restores numbers but not function of B-1 lymphocytes in xid mice.
Mice expressing the X-linked immunodeficiency (xid) mutation lack functional Bruton's tyrosine kinase and were shown to be specifically deficient in peritoneal B-1 lymphocytes. We have previously shown that IL-9, a cytokine produced by TH2 lymphocytes, promotes B-1 cell expansion in vivo. To determine whether IL-9 overexpression might compensate the xid mutation for B-1 lymphocyte development, we crossed xid mice with IL-9-transgenic mice. In this model, IL-9 restored normal numbers of mature peritoneal B-1 cells that all belonged to the CD5(-) B-1b subset. Despite this normal B-1 lymphocyte number, IL-9 failed to restore classical functions of B-1 cells, namely, the production of natural IgM Abs, the T15 Id Ab response to phosphorylcholine immunization, and the antipolysaccharide humoral response against Streptococcus pneumoniae. By using bromelain-treated RBC, we showed that the antigenic repertoire of these IL-9-induced B-1b lymphocytes was different from the repertoire of classical CD5(+) B-1a cells, indicating that the lack of B-1 function by B-1b cells is associated with distinct Ag specificities. Taken together, our data show that B-1b cell development can restore the peritoneal B-1 population in xid mice but that these B-1b cells are functionally distinct from CD5(+) B-1a lymphocytes.
Knoops
Laurent
L
Ludwig Institute for Cancer Research and Experimental Medicine Unit, Université de Louvain, Brussels, Belgium.
Louahed
Jamila
J
Renauld
Jean-Christophe
JC
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018956:CD5 Antigens / Q000096:biosynthesis; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D005260:Female; D007075:Immunoglobulin M / Q000378:metabolism; D016906:Interleukin-9 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010767:Phosphorylcholine / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D013211:Staphylococcus aureus / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D018956:CD5 Antigens; D007075:Immunoglobulin M; D016906:Interleukin-9; D011135:Polysaccharides, Bacterial; D010767:Phosphorylcholine; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse