title: B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS.
abstract: B-1 cells mediate early protection against infection by responding to T cell-independent (TI) antigens found on the surface of various pathogens. Mice with impaired expression of the atypical IκB protein IκBNS have markedly reduced frequencies of B-1 cells. We used a mouse strain with dysfunctional IκBNS derived from an N-ethyl-N-nitrosourea (ENU) screen, named bumble, to investigate the point in the development of B-1 cells where IκBNS is required. The presence of wild-type (wt) peritoneal cells in mixed wt/bumble chimeras did not rescue the development of bumble B-1 cells, but wt peritoneal cells transferred to bumble mice restored natural IgM levels and response to TI antigens. The bumble and wt mice displayed similar levels of fetal liver B-1 progenitors and splenic neonatal transitional B (TrB) cells, both of which were previously shown to give rise to B-1 cells. Interestingly, we found that a subset of wt neonatal TrB cells expressed common B-1a markers (TrB-1a) and that this cell population was absent in the bumble neonatal spleen. Sorted TrB-1a (CD93(+)IgM(+)CD5(+)) cells exclusively generated B-1a cells when adoptively transferred, whereas sorted CD93(+)IgM(+)CD5(-) cells gave rise to B-2 cells and, to a lesser extent, B-1b and B-1a cells. This study identifies a phenotypically distinct splenic population of TrB-1a cells and establishes that the development of B-1a cells is blocked before this stage in the absence of IκBNS.
authors.affiliation: Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; and.
authors.forename: Gabriel K
authors.initials: GK
authors.lastname: Pedersen
authors.affiliation: Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; and.
authors.forename: Monika
authors.initials: M
authors.lastname: Àdori
authors.affiliation: Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; and.
authors.forename: Sharesta
authors.initials: S
authors.lastname: Khoenkhoen
authors.affiliation: Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; and.
authors.forename: Pia
authors.initials: P
authors.lastname: Dosenovic
authors.affiliation: Center for Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390-8505 bruce.beutler@utsouthwestern.edu gunilla.karlsson.hedestam@ki.se.
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
authors.affiliation: Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; and bruce.beutler@utsouthwestern.edu gunilla.karlsson.hedestam@ki.se.
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Karlsson Hedestam
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D000955:Antigens, T-Independent / Q000008:administration & dosage; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D020672:I-kappa B Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000955:Antigens, T-Independent; D020672:I-kappa B Proteins; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C454819:Nfkbid protein, mouse
keywords: B-1b; IκB-δ; NF-κB1; NP-ficoll; Nfkbid