B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS
| Autor: | Bruce Beutler, Gunilla B. Karlsson Hedestam, Gabriel K. Pedersen, Sharesta Khoenkhoen, Pia Dosenovic, Monika Adori |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adoptive cell transfer
Cellular differentiation Population B-Lymphocyte Subsets Spleen Biology Mice Antigen medicine Animals education Mice Knockout education.field_of_study Multidisciplinary Intracellular Signaling Peptides and Proteins Proteins Cell Differentiation Molecular biology Adoptive Transfer Antigens T-Independent NFKBID Mice Inbred C57BL medicine.anatomical_structure Phenotype Animals Newborn Immunoglobulin M PNAS Plus biology.protein I-kappa B Proteins CD5 |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 111(39) |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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