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Themis2: setting the threshold for B-cell selection

Cellular & Molecular Immunology volume 14, pages 643–645 (2017)Cite this article

The strength of signal downstream of the B-cell receptor (BCR) determines the positive and negative selection of B cells. Expression of a functional BCR is required for the selection of immature B cells into the peripheral repertoire in the absence of antigen; but selection is also modulated by avidity and affinity-dependent interactions with self and foreign antigens. These antigen-dependent events shape the B-cell repertoire during ontogeny, development and the response to pathogens, and generation of B-cell memory; however, the mechanisms underlying these processes are not very well understood.

During early ontogeny, interactions with intracellular or low abundance self-antigens allow positive selection of innate-like B1 B cells.1 In contrast, the presence of abundant soluble or low-avidity self-antigen leads to B-cell anergy, whereas stronger signals from highly abundant or multivalent antigens trigger receptor editing and/or negative selection of immature B cells through central tolerance.2 These processes must be determined by the state and environment of the B cells, defined in part by the presence of co-stimulation or other signals. Later in the periphery, antigens of similar affinity or avidity elicit B-cell activation, leading to rapid proliferation, plasma cell differentiation and antibody production. During an immune response to pathogens, the majority of B-cell activation involves interactions with lower avidity and/or low-affinity antigens in a soluble, potentially tolerogenic form or coupled via complement or Fc receptors, notably arrayed on the membranes of macrophages, B cells and follicular dendritic cells.3, 4 However, despite the importance of antigen quality and quantity in modulating B-cell responses, very little is understood about the process that defines the signalling threshold between positive and negative selection, allowing B cells to discriminate between antigens of varying strength and form.

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  1. Nuffield Department of Medicine, MRC Human Immunology Unit, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK

    Mukta Deobagkar-Lele, Consuelo Anzilotti & Richard J Cornall

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  1. Mukta Deobagkar-Lele
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  2. Consuelo Anzilotti
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  3. Richard J Cornall
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Correspondence to Richard J Cornall.

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Deobagkar-Lele, M., Anzilotti, C. & Cornall, R. Themis2: setting the threshold for B-cell selection. Cell Mol Immunol 14, 643–645 (2017). https://doi.org/10.1038/cmi.2017.27

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