Altered Marginal Zone B Cell Selection in the Absence of IκBNS

• Published in: The Journal of immunology (1950) 2018-01, Vol.200 (2), p.775-787
• Main Authors: Ádori, Monika, Pedersen, Gabriel K, Ádori, Csaba, Erikson, Elina, Khoenkhoen, Sharesta, Stark, Julian M, Choi, Jin Huk, Dosenovic, Pia, Karlsson, Mikael C I, Beutler, Bruce, Karlsson Hedestam, Gunilla B
• Format: Article
• Language: English
• Subjects: Bone marrow; Cell differentiation; Chimeras; Flow cytometry; Immune response (humoral); Immunization; Lipopolysaccharides; Lymphocyte receptors; Lymphocytes B; Lymphocytes T; Mice; Spleen; Surface markers
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1700791

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 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 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 mice revealed no alteration in the cellular MZ microenvironment, and analysis of bone marrow chimeras indicated that the MZ B cell development defect in mice was B cell intrinsic. Further, we demonstrate that the B cells that repopulate the MZ in aged 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 mice. Finally, plasma cell differentiation of sorted LPS-stimulated MZ B cells was impaired, and aged 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.