Altered Marginal Zone B Cell Selection in the Absence of i κbNS

Monika Ádori, Gabriel K. Pedersen, Csaba Ádori, Elina Erikson, Sharesta Khoenkhoen, Julian M. Stark, Jin Huk Choi, Pia Dosenovic, Mikael C.I. Karlsson, Bruce Beutler, Gunilla B.Karlsson Hedestam

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Abstract

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. IkBNS-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 IkBNS. 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 IkBNS is required for an intact MZ B cell compartment in C57BL/6 mice.

Original languageEnglish (US)
Pages (from-to)775-787
Number of pages13
JournalJournal of Immunology
Volume200
Issue number2
DOIs
StatePublished - Jan 15 2018

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ASJC Scopus subject areas

  • Immunology

Cite this

Ádori, M., Pedersen, G. K., Ádori, C., Erikson, E., Khoenkhoen, S., Stark, J. M., Choi, J. H., Dosenovic, P., Karlsson, M. C. I., Beutler, B., & Hedestam, G. B. K. (2018). Altered Marginal Zone B Cell Selection in the Absence of i κbNS. Journal of Immunology, 200(2), 775-787. https://doi.org/10.4049/jimmunol.1700791