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IKKα deficiency disrupts the development of marginal zone and follicular B cells

Genes & Immunityvolume 20pages224233 (2019) | Download Citation


Only few genes have been confidently identified to be involved in the Follicular (FO) and Marginal Zone (MZ) B cell differentiation, migration, and retention in the periphery. Our group previously observed that IKKα kinase inactive mutant mice IKKαK44A/K44A have significantly lower number of MZ B cells whereas FO B cell numbers appeared relatively normal. Because kinase dead IKKα can retain some of its biological functions that may interfere in revealing its actual role in the MZ and FO B cell differentiation. Therefore, in the current study, we genetically deleted IKKα from the pro-B cell lineage that revealed novel functions of IKKα in the MZ and FO B lymphocyte development. The loss of IKKα produces a significant decline in the percentage of immature B lymphocytes, mature marginal zone B cells, and follicular B cells along with a severe disruption of splenic architecture of marginal and follicular zones. IKKα deficiency affect the recirculation of mature B cells through bone marrow. A transplant of IKKα knockout fetal liver cells into Rag−/− mice shows a significant reduction compared to control in the B cells recirculating through bone marrow. To reveal the genes important in the B cell migration, a high throughput gene expression analysis was performed on the IKKα deficient recirculating mature B cells (B220+IgMhi). That revealed significant changes in the expression of genes involved in the B lymphocyte survival, homing and migration. And several among those genes identified belong to G protein family. Taken together, this study demonstrates that IKKα forms a vial axis controlling the genes involved in MZ and FO B cell differentiation and migration.

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Additional information

Data deposition:The microarray data was deposited in NCBI Gene Expression Omnibus (GEO) under accession number GSE102587.


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Author contributions

MYB and JWB performed all experiments. GW did the Immunofluorescence assays. MYB and YH oversaw the experimental design and data interpretation; and MYB wrote the manuscript.

Author information


  1. Division of Hematology/Oncology, Department of Medicine, Tufts University School of Medicine, Boston, MA, USA

    • Mumtaz Y. Balkhi
  2. Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institute of Health, Frederick, MD, USA

    • Jami Willette-Brown
    •  & Yinling Hu
  3. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Tufts University School of Medicine, Boston, MA, USA

    • Gabor Wittmann


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The authors declare that they have no conflict of interest.

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Correspondence to Mumtaz Y. Balkhi.

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