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The BCR-SEQC initiative

Nature Immunology volume 26, pages 978–979 (2025)Cite this article

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B cells express a diverse repertoire of antigen receptors known as B cell receptors (BCRs). BCR proteins are composed of two identical heavy chains (IGH) and two identical light chains (IGK or IGL). BCR diversity is generated by V(D)J recombination, assembling V, D and J gene segments for the heavy chain or V and J segments for the light chain. Further diversification occurs via nucleotide addition and deletion at junctions between the recombining gene segments. The third complementarity-determining region (CDR3) of IGH is the most diverse part of the BCR and serves as a clonal marker. After BCR assembly in the bone marrow, B cells migrate to peripheral lymphoid organs to participate in immune responses. Here, BCRs undergo further modification by somatic hypermutation (SHM) and class-switch recombination (for example, from IgM to IgG, IgA or IgE). These processes refine BCR specificity and function1.

Adaptive immune receptor repertoire profiling (AIRR-seq) is performed by next-generation sequencing of BCR and T cell receptor (TCR) gene rearrangements2. AIRR-seq can evaluate hundreds to billions of antigen receptors per individual. Profiling blood, bone marrow or lymph node samples can reveal B cell clones associated with responses to vaccines, self (autoimmunity), or sizable expansions linked to lymphoid malignancies. Longitudinal sampling further enables the study of clonal recruitment and intraclonal diversification in response to specific antigens.

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References

  1. Chi, X. et al. Immunology 160, 233–247 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Marquez, S. et al. Methods Mol. Biol. 2453, 297–316 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Baines, A. C. et al. Clin. Cancer Res. 29, 2748–2752 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Rubelt, F. et al. Nat. Immunol. 18, 1274–1278 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Trück, J. et al. Elife 10, e66274 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Xiao, W. Zenodo https://doi.org/10.5281/zenodo.15359757 (2025).

Download references

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Authors and Affiliations

  1. Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA

    Rittika Mallik, Andrea C. Baines, Marc R. Theoret & Wenming Xiao

  2. Cellino Bio, Cambridge, MA, USA

    Rebecca Kusko

  3. Oncology Center of Excellence, US Food and Drug Administration, Silver Spring, MD, USA

    Reena Philip & Marc R. Theoret

  4. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Eline T. Luning Prak

Authors
  1. Rittika Mallik
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  2. Rebecca Kusko
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  3. Andrea C. Baines
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  4. Reena Philip
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  5. Marc R. Theoret
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  6. Eline T. Luning Prak
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  7. Wenming Xiao
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Corresponding authors

Correspondence to Eline T. Luning Prak or Wenming Xiao.

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This publication reflects the views of the authors and should not be construed to represent FDA’s views or policies. All authors claim no conflicts of interest.

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Mallik, R., Kusko, R., Baines, A.C. et al. The BCR-SEQC initiative. Nat Immunol 26, 978–979 (2025). https://doi.org/10.1038/s41590-025-02196-6

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