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

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

Research output: Article

1 Citation (Scopus)

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
Pages (from-to)775-787
Number of pages13
JournalJournal of Immunology
Volume200
Issue number2
DOIs
Publication statusPublished - jan. 15 2018

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B-Lymphocytes
Blood-Borne Pathogens
B-Lymphocyte Subsets
Ficoll
B-Lymphoid Precursor Cells
Humoral Immunity
Plasma Cells
Inbred C57BL Mouse
Cell Differentiation
Immunization
Flow Cytometry
Spleen
Bone Marrow
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Ádori, M., Pedersen, G. K., Ádori, C., Erikson, E., Khoenkhoen, S., Stark, J. M., ... 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

Altered Marginal Zone B Cell Selection in the Absence of i κbNS. / Ádori, Monika; Pedersen, Gabriel K.; Ádori, C.; Erikson, Elina; Khoenkhoen, Sharesta; Stark, Julian M.; Choi, Jin Huk; Dosenovic, Pia; Karlsson, Mikael C.I.; Beutler, Bruce; Hedestam, Gunilla B.Karlsson.

In: Journal of Immunology, Vol. 200, No. 2, 15.01.2018, p. 775-787.

Research output: Article

Ádori, M, Pedersen, GK, Ádori, C, Erikson, E, Khoenkhoen, S, Stark, JM, Choi, JH, Dosenovic, P, Karlsson, MCI, Beutler, B & Hedestam, GBK 2018, 'Altered Marginal Zone B Cell Selection in the Absence of i κbNS', Journal of Immunology, vol. 200, no. 2, pp. 775-787. https://doi.org/10.4049/jimmunol.1700791
Ádori M, Pedersen GK, Ádori C, Erikson E, Khoenkhoen S, Stark JM et al. Altered Marginal Zone B Cell Selection in the Absence of i κbNS. Journal of Immunology. 2018 jan. 15;200(2):775-787. https://doi.org/10.4049/jimmunol.1700791
Ádori, Monika ; Pedersen, Gabriel K. ; Ádori, C. ; Erikson, Elina ; Khoenkhoen, Sharesta ; Stark, Julian M. ; Choi, Jin Huk ; Dosenovic, Pia ; Karlsson, Mikael C.I. ; Beutler, Bruce ; Hedestam, Gunilla B.Karlsson. / Altered Marginal Zone B Cell Selection in the Absence of i κbNS. In: Journal of Immunology. 2018 ; Vol. 200, No. 2. pp. 775-787.
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AU - Khoenkhoen, Sharesta

AU - Stark, Julian M.

AU - Choi, Jin Huk

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