Age-Associated B Cells Correlate with Impaired Immune Response

Age-associated B cells are one of a number of dysfunctional or maladaptive immune cell subpopulations that appear in increasing numbers in later late, and which likely impair the many functions of the immune system by their presence. Clearing all B cells rather than trying to selectively clear age-associated B cells is a viable proposition, as the B cell population regenerates quite rapidly following clearance, and the new cells lack the age-associated B cell phenotype. This has been demonstrated in animal models, but has yet to make it to the clinic as a treatment to improve the aged immune system.

Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response.

Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2.

ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination.


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