Altered Marginal Zone B Cell Selection in the Absence of IκBNS

J Immunol. 2018 Jan 15;200(2):775-787. doi: 10.4049/jimmunol.1700791. Epub 2017 Dec 8.


Marginal zone (MZ) B cells reside in the splenic MZ and play important roles in T cell-independent humoral immune responses against blood-borne pathogens. IκBNS-deficient bumble mice exhibit a severe reduction in the MZ B compartment but regain an MZ B population with age and, thus, represent a valuable model to examine the biology of MZ B cells. In this article, we characterized the MZ B cell defect in further detail and investigated the nature of the B cells that appear in the MZ of aged bumble mice. Flow cytometry analysis of the splenic transitional B cell subsets demonstrated that MZ B cell development was blocked at the transitional-1 to transitional-2-MZ precursor stage in the absence of functional IκBNS. Immunohistochemical analysis of spleen sections from wild-type and bumble mice revealed no alteration in the cellular MZ microenvironment, and analysis of bone marrow chimeras indicated that the MZ B cell development defect in bumble mice was B cell intrinsic. Further, we demonstrate that the B cells that repopulate the MZ in aged bumble mice were distinct from age-matched wild-type MZ B cells. Specifically, the expression of surface markers characteristic for MZ B cells was altered and the L chain Igλ+ repertoire was reduced in bumble mice. Finally, plasma cell differentiation of sorted LPS-stimulated MZ B cells was impaired, and aged bumble mice were unable to respond to NP-Ficoll immunization. These results demonstrate that IκBNS is required for an intact MZ B cell compartment in C57BL/6 mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Antigens, T-Independent / immunology
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism*
  • Biomarkers
  • Cell Differentiation
  • Clonal Selection, Antigen-Mediated*
  • I-kappa B Kinase / deficiency*
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Immunophenotyping
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Knockout
  • Phenotype
  • Spleen / immunology*
  • Spleen / metabolism*


  • Antigens, T-Independent
  • Biomarkers
  • Immunoglobulin G
  • Lipopolysaccharides
  • I-kappa B Kinase