First Author | Ádori M | Year | 2018 |
Journal | J Immunol | Volume | 200 |
Issue | 2 | Pages | 775-787 |
PubMed ID | 29222168 | Mgi Jnum | J:253599 |
Mgi Id | MGI:6110242 | Doi | 10.4049/jimmunol.1700791 |
Citation | Adori M, et al. (2018) Altered Marginal Zone B Cell Selection in the Absence of IkappaBNS. J Immunol 200(2):775-787 |
abstractText | 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. IkappaBNS-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 IkappaBNS. 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 Iglambda(+) 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 IkappaBNS is required for an intact MZ B cell compartment in C57BL/6 mice. |