Age-Associated B Cells Contribute to Autoimmunity and Chronic Inflammation – Innovita Research

Age-Associated B Cells Contribute to Autoimmunity and Chronic Inflammation

The immune system becomes disordered and dysfunctional with age in numerous different ways. The B cell component accumulates inflammatory and problematic cells that are known as age-associated B cells. Here, researchers show that these errant B cells produce antibodies that provoke autoimmunity.

B cell aging is a problem with a solution demonstrated in animal models: just destroy all B cells. Mammals can get by without B cells for at least a short period of time, and the B cell population regenerates quite rapidly following clearance even in later life. The newly replaced B cells do not exhibit the problems of their destroyed predecessors, improving immune function as a result. There is still too little movement when it comes to adapting this approach for human medicine, alas.

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Aging is associated with increased intrinsic B cell inflammation, decreased protective antibody responses and increased autoimmune antibody responses. The effects of aging on the metabolic phenotype of B cells and on the metabolic programs that lead to the secretion of protective versus autoimmune antibodies are not known. In this paper we evaluated the metabolic profile of B cells isolated from the spleens of young and old mice, with the aim to identify metabolic pathways associated with intrinsic B cell inflammation and with the secretion of autoimmune antibodies.

We focused on the secretion of autoimmune antibodies because our recent human B cell results have shown that higher intrinsic inflammation in unstimulated B cells from elderly individuals induces a “pre-activation” status associated with the secretion of IgG antibodies with autoimmune specificities, similar to what has been observed in autoimmune diseases. In order to identify the B cell subsets driving the phenotype and function of B cells in the splenic B cell pool of old mice, we sorted the major splenic B cell subsets, Follicular (FO) B cells and Age-associated B cells (ABCs).

Results have shown that ABCs are the cells driving the phenotype and function of B cells in the spleen of old mice. Hyper-inflammatory ABCs from old mice are also hyper-metabolic and supported by a specific metabolic profile needed not only to support intrinsic inflammation but also autoimmune antibody secretion. Our results allow the identification of a relationship between intrinsic inflammation, metabolism and autoimmune B cells, advancing our understanding of critical mechanisms leading to the generation of pathogenic B cells.

Pathogenic B cells that are hyper-inflammatory and secrete autoimmune antibodies can also induce pro-inflammatory T cells in both mice and humans, and it has been shown that immunotherapy of autoimmune (rheumatoid arthritis) patients with anti-CD20 antibody not only specifically depletes B cells, but also blocks glucose uptake and usage in T cells and impairs the differentiation of pathogenic T cells, leading to an improved health condition.

Link: https://doi.org/10.1186/s12979-021-00222-3

Source: Fight Aging!