Molecular and Cellular Analysis of Autoreactive B Cell Elimination from Germinal

$61,241P30FY2012ARNIH

Washington University, Saint Louis MO

Investigators

Linked publications & trials

Paper 39209843 Paper 38861030 Paper 36136607 Paper 35762854 Paper 34997119 Paper 33858961 Paper 33010224 Paper 32759496 Paper 31926267 Paper 31453341 Paper 31133752 Paper 30679644 Paper 30656721 Paper 30642904 Paper 30556808 Paper 30156437 Paper 29924462 Paper 29850891 Paper 29848759 Paper 29531168 Paper 29496999 Paper 29339260 Paper 29292385 Paper 29246946 Paper 28923946 Paper 28698274 Paper 28652462 Paper 28501330 Paper 28196665 Paper 28192370 Paper 28134626 Paper 28077655 Paper 27827374 Paper 27798558 Paper 27782327 Paper 27758872 Paper 27655849 Paper 27650575 Paper 27645461 Paper 27572114 Paper 27566940 Paper 27463423 Paper 27440901 Paper 27384652 Paper 27374498 Paper 27295359 Paper 27283739 Paper 27282141 Paper 27194724 Paper 27193971 Paper 27107939 Paper 27013439 Paper 26927668 Paper 26914463 Paper 26878062 Paper 26764599 Paper 26720279 Paper 26680205 Paper 26675068 Paper 26501415 Paper 26471127 Paper 26320659 Paper 26280891 Paper 26268657 Paper 26197390 Paper 26045138 Paper 25788521 Paper 25723276 Paper 25686606 Paper 25605921 Paper 25605621 Paper 25595780 Paper 25587897 Paper 25531075 Paper 25482432 Paper 25451972 Paper 25428507 Paper 25367577 Paper 25359994 Paper 25320315 Paper 25205096 Paper 25189337 Paper 25150608 Paper 25034031 Paper 25029552 Paper 25019227 Paper 25016574 Paper 25005358 Paper 24931121 Paper 24913981 Paper 24899198 Paper 24847005 Paper 24794230 Paper 24743949 Paper 24714492 Paper 24711582 Paper 24658051 Paper 24598588 Paper 24569377 Paper 24531241

Abstract

Self-reactivity in antibodies isolated from patients with autoimmune disorders is often imparted by somatic mutations. Indeed, reversion of immunoglobulin genes to germ line sequences typically eliminates reactivity against self-antigens. These data suggest that many autoreactive B cells are derived from the germinal center reaction, in which somatic hypermutation of immunoglobulin variable genes occurs. The mechanisms by which self-reactive B cells are eliminated during early development are well-understood. In contrast, very little is known about how somatic mutation-induced self-reactivity is normally prevented in healthy individuals, and which of these pathways fail in patients with autoimmune disorders. In this proposal, we will identify the survival pathways downstream of B cell receptor (BCR) signals and CD4+ T cell help that allow autoreactive B cells to survive.

View original record on NIH RePORTER →