A rheostat sets B-cell receptor repertoire selection to distinguish self from non-self. (December 2020)

• Record Type: Journal Article
• Authors: Jani, Peter K; Kubagawa, Hiromi; Melchers, Fritz
• Is Part Of: Current opinion in immunology. Volume 67(2020)
• Page Start: 42
• Page End: 49
• Publication Date: 2020-12
• Subjects: Immunology -- Periodicals; Allergy -- Periodicals; Immunology -- Abstracts -- Periodicals; Allergy -- Abstracts -- Periodicals; 616.079
• DOI: 10.1016/j.coi.2020.07.003
• Languages: English
• ISSNs: 0952-7915

Abstract

Highlights: 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. Abstract : 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.