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

Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):E4119-26. doi: 10.1073/pnas.1415866111. Epub 2014 Sep 16.


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.

Keywords: B-1b; IκB-δ; NF-κB1; NP-ficoll; Nfkbid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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