Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Sep 11;15(9):e17341.
doi: 10.15252/emmm.202217341. Epub 2023 Jun 5.

Functions of double-negative B cells in autoimmune diseases, infections, and cancers

Affiliations
Review

Functions of double-negative B cells in autoimmune diseases, infections, and cancers

Michael King Yung Chung et al. EMBO Mol Med. .

Abstract

Most mature B cells can be divided into four subtypes based on the expression of the surface markers IgD and CD27: IgD+ CD27- naïve B cells, IgD+ CD27+ unswitched memory B cells, IgD- CD27+ switched memory B cells, and IgD- CD27- double-negative (DN) B cells. Despite their small population size in normal peripheral blood, DN B cells play integral roles in various diseases. For example, they generate autoimmunity in autoimmune conditions, while these cells may generate both autoimmune and antipathogenic responses in COVID-19, or act in a purely antipathogenic capacity in malaria. Recently, DN B cells have been identified in nasopharyngeal carcinoma and non-small-cell lung cancers, where they may play an immunosuppressive role. The distinct functions that DN B cells play in different diseases suggest that they are a heterogeneous B-cell population. Therefore, further study of the mechanisms underlying the involvement of DN B cells in these diseases is essential for understanding their pathogenesis and the development of therapeutic strategies. Further research is thus warranted to characterize the DN B-cell population in detail.

Keywords: COVID-19; autoimmune disease; cancer immunosuppression; double-negative B cells; tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1. Hypothesized trajectories of B‐cell development into different subtypes of DN B cells
DN1 and DN4 B cells are suspected to be precursors of class‐switched memory cells (Stewart et al, 2021). Moreover, DN2 B cells can differentiate into ASCs, and “activated naïve” B cells plus DN3 B cells have been suggested as potential DN2 B‐cell precursors (Jenks et al, ; Stewart et al, 2021). Although DN2 B cells have been suggested to be on an alternate developmental pathway from switched memory B cells (Jenks et al, 2018), GC‐derived memory B cells may gain features associated with DN2 B cells under inflammatory conditions and develop into DN2‐like “atypical B cells” in malaria, which will be discussed further below (Ambegaonkar et al, ; Holla et al, 2021). Due to the ambiguity surrounding the developmental site of DN2 B cells, the above findings surrounding “atypical B cells” opens the possibility of GC involvement in DN2 B development. More research is needed to fully uncover the developmental pathways of different DN B cells.

References

    1. Akkaya M, Kwak K, Pierce SK (2020) B cell memory: building two walls of protection against pathogens. Nat Rev Immunol 20: 229–238 - PMC - PubMed
    1. Alexandrov LB, Nik‐Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Børresen‐Dale AL et al (2013) Signatures of mutational processes in human cancer. Nature 500: 415–421 - PMC - PubMed
    1. Ambegaonkar AA, Nagata S, Pierce SK, Sohn H (2019) The differentiation in vitro of human tonsil B cells with the phenotypic and functional characteristics of T‐bet+ atypical memory B cells in malaria. Front Immunol 10: 852 - PMC - PubMed
    1. Ambegaonkar AA, Kwak K, Sohn H, Manzella‐Lapeira J, Brzostowski J, Pierce SK (2020) Expression of inhibitory receptors by B cells in chronic human infectious diseases restricts responses to membrane‐associated antigens. Sci Adv 6: eaba6493 - PMC - PubMed
    1. Anders H‐J, Saxena R, Zhao M‐H, Parodis I, Salmon JE, Mohan C (2020) Lupus nephritis. Nat Rev Dis Primers 6: 7 - PubMed

Publication types