TY - JOUR
T1 - Altered Marginal Zone B Cell Selection in the Absence of i κbNS
AU - Ádori, Monika
AU - Pedersen, Gabriel K.
AU - Ádori, Csaba
AU - Erikson, Elina
AU - Khoenkhoen, Sharesta
AU - Stark, Julian M.
AU - Choi, Jin Huk
AU - Dosenovic, Pia
AU - Karlsson, Mikael C.I.
AU - Beutler, Bruce
AU - Hedestam, Gunilla B.Karlsson
N1 - Funding Information:
This work was supported by a grant from the Swedish Research Foundation (to G.B.K.H.).
Publisher Copyright:
Copyright © 2018 by The American Association of Immunologists, Inc.
PY - 2018/1/15
Y1 - 2018/1/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85044713250&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044713250&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1700791
DO - 10.4049/jimmunol.1700791
M3 - Article
C2 - 29222168
AN - SCOPUS:85044713250
SN - 0022-1767
VL - 200
SP - 775
EP - 787
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -