Altered Marginal Zone B Cell Selection in the Absence of IκBNS
| Autor: | Bruce Beutler, Csaba Adori, Mikael C. I. Karlsson, Gunilla B. Karlsson Hedestam, Elina Erikson, Monika Adori, Julian M. Stark, Gabriel K. Pedersen, Pia Dosenovic, Jin Huk Choi, Sharesta Khoenkhoen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Cellular differentiation Immunology Population B-Lymphocyte Subsets Spleen Biology Immunophenotyping 03 medical and health sciences Mice 0302 clinical medicine Marginal zone B-cell Plasma cell differentiation medicine Immunology and Allergy Animals education Clonal Selection Antigen-Mediated B cell Mice Knockout education.field_of_study Age Factors Cell Differentiation Marginal zone Molecular biology Antigens T-Independent I-kappa B Kinase 030104 developmental biology medicine.anatomical_structure Phenotype Immunoglobulin G Biomarkers 030215 immunology |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 200(2) |
| ISSN: | 1550-6606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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