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Self-Reactive B Cells in the Germinal Center Reaction


Maintenance of immunological self-tolerance requires lymphocytes carrying self-reactive antigen receptors to be selectively prevented from mounting destructive or inflammatory effector responses. Classically, self-tolerance is viewed in terms of the removal, editing, or silencing of B and T cells that have formed self-reactive antigen receptors during their early development. However, B cells activated by foreign antigen can enter germinal centers (GCs), where they further modify their antigen receptor by somatic hypermutation (SHM) of their immunoglobulin genes. The inevitable emergence of activated, self-reactive GC B cells presents a unique challenge to the maintenance of self-tolerance that must be rapidly countered to avoid autoantibody production. Here we discuss current knowledge of the mechanisms that enforce B cell self-tolerance, with particular focus on the control of self-reactive GC B cells. We also consider how self-reactive GC B cells can escape self-tolerance to initiate autoantibody production or instead be redeemed via SHM and used in productive antibody responses.

Type Journal
ISBN 1545-3278 (Electronic) 0732-0582 (Linking)
Authors Brink, R.; Phan, T. G.
Responsible Garvan Author Prof Robert Brink
Publisher Name Annual Review of Immunology
Published Date 2018-04-01
Published Volume 36
Published Pages 339-357
Status Published in-print
DOI 10.1146/annurev-immunol-051116-052510
URL link to publisher's version