A rheostat sets B-cell receptor repertoire selection to distinguish self from non-self

• Published in: Current opinion in immunology Vol. 67; pp. 42 - 49
• Main Authors: Jani, Peter K, Kubagawa, Hiromi, Melchers, Fritz
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2020
• ISSN: 0952-7915; 1879-0372
• DOI: 10.1016/j.coi.2020.07.003

•BcRs bind self or non-self antigens with spectra of high to low to no avidities.•A BcR-antigen-IgM-FcμR-rheostat sets PI3K-PTEN balanced B cell signaling.•Hypermutated IgG autoantibodies derive from self/non-self cross-reactive BcR.
In bone marrow VDJ-recombination continuously generates original repertoires of immature B cells expressing IgM-B cell receptor (BcR), in which each cell recognizes the wide variety of self and non-self antigens with an individually different spectrum of avidities. High avidity self-reactive B cells try to edit their BcRs by secondary or multiple VL-rearrangements to JL-rearrangements. If they do not manage to change their self reactivity, they are deleted by apoptosis. Low avidity self-reactive B cells are anergized, while B cells with no avidity to self are ignored. A rheostat crosslinking antigen-binding BcRs, self antigen complexed with pentameric IgM and Fcμ-receptor monitors high, low or no binding. PI3K and PTEN are the effectors of this self antigen-sensing device. In mature B cells this rheostat continues to function in the activation of resting B cells by foreign antigens which crosslink BcR, antigen and pentameric IgM with Fcμ-receptors.