Redemption of autoantibodies on anergic B cells by variable-region glycosylation and mutation away from self-reactivity.

ABSTRACT: The best-understood mechanisms for achieving antibody self/non-self discrimination discard self-reactive antibodies before they can be tested for binding microbial antigens, potentially creating holes in the repertoire. Here we provide evidence for a complementary mechanism: retaining autoantibodies in the repertoire displayed as low levels of IgM and high IgD on anergic B cells, masking a varying proportion of autoantibody-binding sites with carbohydrates, and removing their self-reactivity by somatic hypermutation and selection in germinal centers (GCs). Analysis of human antibody sequences by deep sequencing of isotype-switched memory B cells or in IgG antibodies elicited against allogeneic RhD+ erythrocytes, vaccinia virus, rotavirus, or tetanus toxoid provides evidence for reactivatio

SUBMITTER: Sabouri Z 

PROVIDER: S-EPMC4078846 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature