Differences in self-recognition between secreted antibody and membrane-bound B cell antigen receptor

The random gene segment rearrangement during B cell development ensures Ab repertoire diversity. Because this process might generate autoreactive specificities, it has been proposed that stringent selection mechanisms prevent the development of autoreactive B cells. However, conventional assays to i...

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Auteurs principaux: Iype, Joseena Mariam (Auteur) , Wardemann, Hedda (Auteur)
Format: Article (Journal)
Langue:anglais
Publié: 25 January 2019
In: The journal of immunology
Year: 2019, Volume: 202, Numéro: 5, Pages: 1417-1427
ISSN:1550-6606
DOI:10.4049/jimmunol.1800690
Accès en ligne:Verlag, Volltext: https://doi.org/10.4049/jimmunol.1800690
Verlag, Volltext: https://www.jimmunol.org/content/202/5/1417
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Notes sur l'auteur:Joseena Iype, Moumita Datta, Ahmad Khadour, Rudolf Übelhart, Antonella Nicolò, Tim Rollenske, Marcus Dühren-von Minden, Hedda Wardemann, Palash C. Maity and Hassan Jumaa
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Résumé:The random gene segment rearrangement during B cell development ensures Ab repertoire diversity. Because this process might generate autoreactive specificities, it has been proposed that stringent selection mechanisms prevent the development of autoreactive B cells. However, conventional assays to identify autoreactive B cells usually employ in vitro-generated Abs, which differ from membrane-bound BCRs. In this study, we used a cell-based assay to investigate the autoreactivity of membrane-bound BCRs derived from different B cell developmental stages of human peripheral blood. Contrasted to soluble Ab counterparts, only a few of the tested BCRs were autoreactive, although the cell-based assay sensitively detects feeble Ag recognition of a germline-reverted murine BCR that was selected after OVA immunization of mice, whereas conventional assays failed to do so. Together, these data suggest that proper identification of autoreactive B cells requires the membrane-bound BCR, as the soluble Ab may largely differ from its BCR counterpart in Ag binding.
Description:Gesehen am 04.09.2019
Description matérielle:Online Resource
ISSN:1550-6606
DOI:10.4049/jimmunol.1800690