Age-associated B cells

Age/autoimmunity-associated B cells (ABCs) are a B cell subpopulation that was first detected in the spleen of older female mice and in autoimmunity-prone mice (Hao Y et al. 2011).

Age-associated B cells (ABCs) are a transcriptionally and functionally well-defined subpopulation of B cells. Age-associated B cells (ABCs) increase in the immune system with age and are therefore found in older individuals as well as in certain chronic infections and autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. How ABCs influence diseases is still unclear (Li ZY et al. 2023). In old age, the proliferation of ABCs may be associated with the following effects:

• Attenuated vaccination responses
• Increased tendency to inflammation ("inflammaging")
• Increased autoimmunity

ABCs proliferate continuously with age and induce the secretion of IL-4/IL-10 as well as Th17 induction, which are associated with autoimmune diseases. Toll-like receptor (TLR)-7 and TLR-9 increase ABC activity. TLR-7/8 and TLR-9 are stimulated by mRNA and DNA vaccines. In contrast to follicular B cells (FoB) and marginal zone B cells (MZB), ABCs are characterized by the expression of myeloid markers and do not divide in response to B cell receptor (BCR) signals (Hao Y et al. 2011).

ABCs secrete autoantibodies upon stimulation in vitro. Their depletion leads to a reduction in autoantibody levels in vivo, suggesting their pathogenic role in the development of autoimmunity (Li ZY et al. 2023).

ABCs are elevated in systemic lupus erythematosus (SLE), systemic scleroderma, Sjögren's syndrome (SS) and multiple sclerosis (MS). ABCs can also be detected in increased amounts in the synovium of RA patients, suggesting a possible role of ABCs in inflammatory arthritis (Qin Y et al. 2022; Phalke S et alk. 2020). The proliferation of CD21low-B cells (a variant of ABCs) has been found in immunodeficiencies (Bakhtiar S et al. 2022).

ABCs can secrete autoreactive antibodies, which is relevant for the pathogenesis of autoimmune diseases. Vaccine-activated ABCs could be involved in autoimmunity. In COVID vaccination, a link between age-associated B cells (ABCs) and autoimmunity after mRNA vaccination was suspected.

Depletion of ABCs reduces the production of IgG and IgG2a. Apart from secreting autoreactive antibodies, ABCs also secrete a variety of cytokines, including IL-4, IL-17, IL-10, IFN-γ and tumor necrosis factor-α (TNF-α).

In addition, ABC-like cells are also elevated in various infectious diseases such as influenza and malaria (Obeng-Adjei N et al. 2017).

1. Bakhtiar S et al. (2022) Regulatory b cells in patients suffering from inborn errors of immunity with severe immune dysregulation. J Autoimmun 132:10289127-10289128.
2. Hao Y et al. (2011) A b-cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood 118:1294-1304).
3. Li ZY et al. (2023) Age/autoimmunity-associated B cells in inflammatory arthritis: An emerging therapeutic target. Front Immunol 14:1103307.
4. Mouat IC et al. (2022) Age-associated B cells in autoimmune diseases. Cell Mol Life Sci 79:402.
5. Obeng-Adjei N et al. (2017) Malaria-induced interferon-γ drives the expansion of tbethi atypical memory b cells. PloS Pathog 13:e100657617- e100657620.
6. Qin Y et al. (2022) Age-associated b cells contribute to the pathogenesis of rheumatoid arthritis by inducing activation of fibroblast-like synoviocytes via TNF-alpha-mediated ERK1/2 and JAK-STAT1 pathways. Ann Rheum Dis 81:1504-1514.
7. Phalke S et alk. (2020) Age-associated b cells appear in patients with granulomatous lung diseases. Am J Respir Crit Care Med 202:1013-1023.