Altered B cell signalling in autoimmunity

Abstract

Recent work has provided new insights into how altered B cell-intrinsic signals — through the B cell receptor (BCR) and key co-receptors — function together to promote the pathogenesis of autoimmunity. These combined signals affect B cells at two distinct stages: first, in the selection of the naive repertoire; and second, during extrafollicular or germinal centre activation responses. Thus, dysregulated signalling can lead to both an altered naive BCR repertoire and the generation of autoantibody-producing B cells. Strikingly, high-affinity autoantibodies predate and predict disease in several autoimmune disorders, including type 1 diabetes and systemic lupus erythematosus. This Review summarizes how, rather than being a downstream consequence of autoreactive T cell activation, dysregulated B cell signalling can function as a primary driver of many human autoimmune diseases.

Induction of brain‐infiltrating T‐bet–expressing B cells in multiple sclerosis

“…This additional effect of CpG-DNA was not found when using sorted memory B cells (see Fig 5B). 10,32 We investigated the effects of IFNγ and CpG-DNA on plasmablast formation and IgG subclass switching during IL-21-/CD40L-induced naive B-cell differentiation. 31 During a germinal center response, naive B cells can either differentiate into plasmablast or memory populations, depending on the local inflammatory environment.…”

“…5,9,10 The presence of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) of MS patients implies that these memory B cells undergo local reactivation (with the help of CD4 + T cells) to further develop into immunoglobulin (Ig)-producing plasmablasts and plasma cells. 5,9,10 The presence of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) of MS patients implies that these memory B cells undergo local reactivation (with the help of CD4 + T cells) to further develop into immunoglobulin (Ig)-producing plasmablasts and plasma cells.…”

Treponema denticola enolase contributes to the production of antibodies against ENO1 but not to the progression of periodontitis

“…During the germinal center reaction, binding to antigens and signaling through the B cell receptors is essential for the selection of the clone and antibody production [31], which may be essential even for autoantibodies. During the antibody response to bacterial antigens in the germinal center, what determines the selection or deselection for B cell clones cross-reactive to autoantigens awaits further clarification.…”

IGHV segment utilization in immunoglobulin gene rearrangement differentiates patients with anti-myelin-associated glycoprotein neuropathy from others immunoglobulin M-gammopathies

“…I ts over-representation has been found in other demyelinating processes 5 such as multiple sclerosis and other autoimmune diseases 14,15 . further studies are needed to address the use of these markers in daily practice.…”

“…In the anti-MAG group, 29 clonotypes were identified for 16 patients: VH4-34 is a human heavy chain family that has germline-encoded polyreactivity towards multiple self-antigens 14 . VH4-34 segment has been identified as a diagnostic marker of variant hairy cell leukemia.…”