Impaired B cell development and function in the absence of IkappaBNS
| Autor: | Derin B. Keskin, Ellis L. Reinherz, Fumiko Shiroki, Linda K. Clayton, Maki Touma, Shigeo Koyasu, Ibuki Saito |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cell type
medicine.medical_treatment Immunology Plasma Cells Enzyme-Linked Immunosorbent Assay Cell Separation Plasma cell Biology Lymphocyte Activation Article Flow cytometry Mice medicine Immunology and Allergy Animals B cell Regulation of gene expression Mice Knockout B-Lymphocytes medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction Intracellular Signaling Peptides and Proteins Proteins Cell Differentiation Marginal zone Flow Cytometry Molecular biology Immunohistochemistry In vitro Mice Inbred C57BL medicine.anatomical_structure Cytokine |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 187(8) |
| ISSN: | 1550-6606 |
| Popis: | IκBNS has been identified as a member of the IκB family of NF-κB inhibitors, which undergoes induction upon TCR signaling. Mice carrying a targeted gene disruption of IκBNS demonstrate dysregulation of cytokines in T cells, macrophages, and dendritic cells. IκBNS mediates both positive and negative gene regulation, depending on individual cell type and/or cytokine. In this study, we demonstrate an additional role for IκBNS in the B cell lineage. B cells from IκBNS knockout (KO) mice were impaired in proliferative responses to LPS and anti-CD40. IgM and IgG3 Igs were drastically reduced in the serum of IκBNS KO mice, although IκBNS KO B cells exhibited a higher level of surface IgM than that found in wild-type mice. Switching to IgG3 was significantly reduced in IκBNS KO B cells. The in vitro induction of plasma cell development demonstrated that progression to Ab-secreting cells was impaired in IκBNS KO B cells. In agreement with this finding, the number of Ab-secreting cells in the spleens of IκBNS KO mice was reduced and production of Ag-specific Igs was lower in IκBNS KO mice after influenza infection as compared with wild-type mice. Additionally, IκBNS KO mice lacked B1 B cells and exhibited a reduction in marginal zone B cells. Thus, IκBNS significantly impacts the development and functions of B cells and plasma cells. |
| Databáze: | OpenAIRE |
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