Formation of B-1 B cells from neonatal B-1 transitional cells exhibits NF-κB redundancy

J Immunol. 2011 Dec 1;187(11):5712-9. doi: 10.4049/jimmunol.1102416. Epub 2011 Oct 26.

Abstract

The stages of development leading up to the formation of mature B-1 cells have not been identified. As a result, there is no basis for understanding why various genetic defects, and those in the classical or alternative NF-κB pathways in particular, differentially affect the B-1 and B-2 B cell lineages. In this article, we demonstrate that B-1 B cells are generated from transitional cell intermediates that emerge in a distinct neonatal wave of development that is sustained for ~2 wk after birth and then declines as B-2 transitional cells predominate. We further show that, in contrast to the dependence of B-2 transitional cells on the alternative pathway, the survival of neonatal B-1 transitional cells and their maturation into B-1 B cells occurs as long as either alternative or classical NF-κB signaling is intact. On the basis of these results, we have generated a model of B-1 development that allows the defects in B-1 and B-2 cell production observed in various NF-κB-deficient strains of mice to be placed into a coherent cellular context.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • B-Lymphocyte Subsets / cytology*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • Cell Differentiation / immunology*
  • Cell Lineage / immunology
  • Cell Separation
  • Flow Cytometry
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Immunohistochemistry
  • Lymphopoiesis / immunology*
  • Mice
  • Mice, Knockout
  • Mice, SCID
  • NF-kappa B / immunology*
  • NF-kappa B / metabolism
  • Signal Transduction / immunology

Substances

  • NF-kappa B