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: Gabriel K Pedersen, Monika Àdori, Sharesta Khoenkhoen, Pia Dosenovic, Bruce Beutler, Gunilla B Karlsson Hedestam
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 111 Issue 39 Pg. E4119-26 (Sep 30 2014) ISSN: 1091-6490 [Electronic] United States
• PMID: 25228759 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, T-Independent
• I-kappa B Proteins
• IkappaBNS protein, mouse
• Immunoglobulin M
• Intracellular Signaling Peptides and Proteins
• Proteins

Topics

• Adoptive Transfer
• Animals
• Animals, Newborn
• Antigens, T-Independent (administration & dosage)
• B-Lymphocyte Subsets (cytology, immunology, metabolism)
• Cell Differentiation (immunology)
• I-kappa B Proteins (deficiency, genetics, immunology)
• Immunoglobulin M (metabolism)
• Intracellular Signaling Peptides and Proteins
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Phenotype
• Proteins (genetics, immunology)