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Immunoglobulin germline gene variation and its impact on human disease

Genes & Immunity volume 22, pages 205–217 (2021)Cite this article

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Abstract

Immunoglobulins (Ig) play an important role in the immune system both when expressed as antigen receptors on the cell surface of B cells and as antibodies secreted into extracellular fluids. The advent of high-throughput sequencing methods has enabled the investigation of human Ig repertoires at unprecedented depth. This has led to the discovery of many previously unreported germline Ig alleles. Moreover, it is becoming clear that convergent and stereotypic antibody responses are common where different individuals recognise defined antigenic epitopes with the use of the same Ig V genes. Thus, germline V gene variation is increasingly being linked to the differential capacity of generating an effective immune response, which might lead to varying disease susceptibility. Here, we review recent evidence of how germline variation in Ig genes impacts the Ig repertoire and its subsequent effects on the adaptive immune response in vaccination, infection, and autoimmunity.

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Fig. 1: Immunoglobulin loci can give rise to antibodies and BCRs with various antigen specificity.
Fig. 2: Different Ig V alleles might affect the immune response.
Fig. 3: Polymorphisms and post-translational modifications in the Ig variable domain can affect antigen binding.
Fig. 4: Differences in germline Ig V alleles affect the immune response.
Fig. 5: Schematic structure of an immunoglobulin V gene.

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Acknowledgements

We thank Benedicte A. Lie and Marte K. Viken (University of Oslo) for providing the numbers displayed in Table 3. We would also like to thank Frode Vartdal (University of Oslo) for a helpful discussion about Ig allotypes. All figures were created with BioRender.com.

Funding

We acknowledge generous support by UiO World-Leading Research Community to VG and LMS, UiO:LifeScience Convergence Environment Immunolingo to VG, EU Horizon 2020 iReceptorplus (#825821) to VG and LMS, a Research Council of Norway FRIPRO project (#300740) to VG, South-Eastern Norway Regional Health Authority (#201611) to LMS and Stiftelsen Kristian Gerhard Jebsen (SKGJ-MED-017, K.G. Jebsen Coeliac Disease Research Centre) to LMS.

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  1. Department of Immunology, University of Oslo, Oslo, Norway

    Ivana Mikocziova, Victor Greiff & Ludvig M. Sollid

  2. K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo and Oslo University Hospital, Oslo, Norway

    Ivana Mikocziova & Ludvig M. Sollid

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  1. Ivana Mikocziova
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Correspondence to Ludvig M. Sollid.

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Mikocziova, I., Greiff, V. & Sollid, L.M. Immunoglobulin germline gene variation and its impact on human disease. Genes Immun 22, 205–217 (2021). https://doi.org/10.1038/s41435-021-00145-5

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