B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS

Gabriel K. Pedersen, Monika Àdori, Sharesta Khoenkhoen, Pia Dosenovic, Bruce Beutler, Gunilla B. Karlsson Hedestam

Research output: Contribution to journalArticle

26 Scopus citations

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-Nnitrosourea (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 whichwere 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.

Original languageEnglish (US)
Pages (from-to)E4119-E4126
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number39
DOIs
StatePublished - Sep 30 2014

Keywords

  • B-1b
  • IκB-δ
  • NF-κB1
  • NP-ficoll
  • Nfkbid

ASJC Scopus subject areas

  • General

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