Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

New insights into the significance of the BCR repertoire in B-1 cell development and function

Cellular & Molecular Immunology volume 16, pages 772–773 (2019)Cite this article

Subjects

As an important player of innate immunity, B-1 cells have been characterized by natural antibody production and rapid immune response. Based on their expression or lack of CD5, B-1 cells are further separated into B-1a and B-1b subsets.1 Although extensive studies have demonstrated a pivotal role of conventional B cells in adaptive immunity, there is increasing evidence indicating the close associations of B-1a cells with self-reactivity, autoimmunity, infection, and even leukemia.2,3,4 Here, we describe recent advances that lead to a clearer understanding of B-1 cell development with a focus on new insights into the significance of the B-cell receptor (BCR) repertoire in B-1a cell biology and discuss the potential strategies for specific targeting of B-1a cells under pathological settings.

B-1a cells have long been known to produce the “natural” antibodies against both self-antigens and general motifs of microbial antigens that are present prior to an infection, but exactly how the BCR repertoire in B-1a cells is selected and shaped remains largely unclear. Using high-dimensional fluorescence-activated cell sorting with quantitative immunoglobulin heavy chain (IgH) deep-sequencing technologies, Yang et al.5 extensively studied the third IgH complementarity-determining region of B-1 and B-2 populations from various organs of mice at different ages. Although the de novo development of B-1 cells in adulthood is largely restricted, the BCR repertoire in B-1a cells from peritoneal cavities and spleens was found to dynamically evolve throughout their ontogeny, reflecting an ongoing selection and/or clonal expansion of the B-1a cell repertoire pool throughout adulthood. Similar repertoire changes in B-1a cells were observed among different individuals even when mice were reared in the absence of microbiota, as revealed by the striking evidence that the B-1a cell repertoire from mice housed in specific pathogen-free and germ-free conditions was indistinguishable. Equally interesting was that activation-induced cytidine deaminase-mediated somatic hypermutation (SHM) was observed after weaning and cumulatively increased with age. This process was associated with class switch recombination but was not driven by microbiota-derived antigens. Since B-1a cells are known to produce anti-self antibodies, these data provide further evidence suggesting that endogenous (self) antigens are possibly the major driving force for repertoire selection. These observations not only support a role for B-1a-derived natural antibodies in maintaining homeostasis but also identify a molecular basis for the notion that age-dependent accumulative SHM may increase the risk of autoimmune disease due to pathogenic high-affinity autoreactive antibodies. From this perspective, the participation of B-1a cells in the first line of host defense may partially result from their cross-reactivity with microorganism-derived antigens, such as the hemagglutinin glycoprotein of influenza virus membrane.6 The sequence data presented in this study offer significant insights into understanding the origins and behaviors of B-1 cells in both hemostasis and autoimmunity, in which increased production of autoantibodies is implicated in the pathogenesis of autoimmune diseases.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Kantor, A. B. The development and repertoire of B-1 cells (CD5 B cells). Immunol. Today 12, 389–391 (1991).

    Article  CAS  Google Scholar 

  2. Sarvaria, A., Madrigal, J. A. & Saudemont, A. B cell regulation in cancer and anti-tumor immunity. Cell Mol. Immunol. 14, 662–674 (2017).

    Article  CAS  Google Scholar 

  3. Smith, F. L. & Baumgarth, N. B-1 cell responses to infections. Curr. Opin. Immunol. 57, 23–31 (2019).

    Article  CAS  Google Scholar 

  4. Wu, H. et al. Epigenetic regulation in B-cell maturation and its dysregulation in autoimmunity. Cell. Mol. Immunol. 15, 676–684 (2018).

    Article  CAS  Google Scholar 

  5. Yang, Y. et al. Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires. Elife. 4, e09083 (2015).

  6. Wang, X. et al. IL-17A promotes pulmonary B-1a cell differentiation via induction of Blimp-1 expression during influenza virus infection. PLoS Pathog. 12, e1005367 (2016).

    Article  Google Scholar 

  7. Graf, R. et al. BCR-dependent lineage plasticity in mature B cells. Science 363, 748–753 (2019).

    Article  CAS  Google Scholar 

  8. Kreslavsky, T. et al. Essential role for the transcription factor Bhlhe41 in regulating the development, self-renewal and BCR repertoire of B-1a cells. Nat. Immunol. 18, 442–455 (2017).

    Article  CAS  Google Scholar 

  9. Samten, B. Regulation of B-1a cells: another novel function of the basic helix-loop-helix transcriptional regulator BHLHE41. Cell. Mol. Immunol. 14, 802–804 (2017).

    Article  CAS  Google Scholar 

  10. Diana, J. et al. Crosstalk between neutrophils, B-1a cells, and plasmacytoid dendritic cells initiates autoimmune diabetes. Nat. Med. 19, 65–73 (2013).

    Article  CAS  Google Scholar 

  11. Deng, J. et al. B1a cells play a pathogenic role in the development of autoimmune arthritis. Oncotarget. 7, 19299–19311 (2016).

  12. Clarke, A. J., Riffelmacher, T., Braas, D., Cornall, R. J. & Simon, A. K. B1a B cells require autophagy for metabolic homeostasis and self-renewal. J. Exp. Med. 215, 399–413 (2018).

    Article  CAS  Google Scholar 

  13. Miller, B. C. et al. The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy 4, 309–314 (2008).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (No. 91842304 and 81771761), the Health and Medical Research Fund, the Food and Health Bureau, the Hong Kong SAR Government, China (No. 17160832), and the Hong Kong Croucher Foundation (260960116).

Author information

Authors and Affiliations

  1. Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China

    Xiaohui Wang, Xiang Lin, Kongyang Ma, Fan Xiao & Liwei Lu

  2. Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Cong Ye & Lingli Dong

Authors
  1. Xiaohui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cong Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiang Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kongyang Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fan Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lingli Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Liwei Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lingli Dong or Liwei Lu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, X., Ye, C., Lin, X. et al. New insights into the significance of the BCR repertoire in B-1 cell development and function. Cell Mol Immunol 16, 772–773 (2019). https://doi.org/10.1038/s41423-019-0249-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41423-019-0249-6

This article is cited by

Search

Advanced search

Quick links