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

Genes & Immunity volume 20, pages 224–233 (2019)Cite this article

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Abstract

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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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.

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Authors and Affiliations

  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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  1. Mumtaz Y. Balkhi
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Correspondence to Mumtaz Y. Balkhi.

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The authors declare that they have no conflict of interest.

Additional information

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

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Balkhi, M.Y., Willette-Brown, J., Wittmann, G. et al. IKKα deficiency disrupts the development of marginal zone and follicular B cells. Genes Immun 20, 224–233 (2019). https://doi.org/10.1038/s41435-018-0025-0

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