Understanding the Heterogeneous Population of Age-Associated B Cells and Their Contributions to Autoimmunity and Immune Response to Pathogens

“An Intrinsic Program Determines Key Age-Associated Changes in Adaptive Immunity That Limit Response to Non-Pathogens”

“…A recently described age-associated B cell (ABC) population, distinguished by lack of CD21 and CD23, accumulates with age (Hao et al, 2011;Rubtsov et al, 2011). We found that in untreated mice, many ABC have a naïve (sIgD + ) phenotype and a small cohort responds to influenza A virus infection, differentiating into plasmablasts and plasma cells that produce influenza-specific Ab (Swain et al, 2017;Kugler-Umana et al, 2020). In fact, we find the immune response to influenza in aged mice is dominated by this T-independent ABC response and it depends heavily on viral recognition mediated by cytoplasmic toll like receptors (TLR) (Swain et al, 2017;Kugler-Umana et al, 2020).…”

“…become more dependent on high levels of pathogen recognition (PR) signals (Jones et al, 2010;Brahmakshatriya et al, 2017), which limits responses except when there are ongoing infections. The responsive naïve B cells in aged mice are also highly dependent on PR (Hao et al, 2011;Rubtsov et al, 2011;Kugler-Umana et al, 2020). We suggest this is a desirable regulatory mechanism to dampen unnecessary immune responses and reduce autoimmunity.…”

“…We found that in untreated mice, many ABC have a naïve (sIgD + ) phenotype and a small cohort responds to influenza A virus infection, differentiating into plasmablasts and plasma cells that produce influenza-specific Ab (Swain et al, 2017;Kugler-Umana et al, 2020). In fact, we find the immune response to influenza in aged mice is dominated by this T-independent ABC response and it depends heavily on viral recognition mediated by cytoplasmic toll like receptors (TLR) (Swain et al, 2017;Kugler-Umana et al, 2020). We are currently extending these studies to determine the potential of sIgD + ABC cell precursors to contribute to protection against influenza.…”

“…ABC also develop in humans in response to infections (Nipper et al, 2018;Kugler-Umana et al, 2020) and they are found associated with autoimmunity (Rubtsov et al, 2013;Rubtsova et al, 2017). Many of the ABC studied in humans and autoimmune mice are non-resting B cells, with non-naïve phenotype, including the most widely studied ABC that express elevated T-Bet and CD11b or CD11c (Rubtsov et al, 2013;Rubtsova et al, 2017;Kugler-Umana et al, 2020).…”

“…ABC also develop in humans in response to infections (Nipper et al, 2018;Kugler-Umana et al, 2020) and they are found associated with autoimmunity (Rubtsov et al, 2013;Rubtsova et al, 2017). Many of the ABC studied in humans and autoimmune mice are non-resting B cells, with non-naïve phenotype, including the most widely studied ABC that express elevated T-Bet and CD11b or CD11c (Rubtsov et al, 2013;Rubtsova et al, 2017;Kugler-Umana et al, 2020). Whether these are derived from the putative naïve ABC that we have characterized is not clear, but all the ABC responses studied so far show strict dependence on TLR7 (Hao et al, 2011;Rubtsov et al, 2011;Rubtsov et al, 2013;Kugler-Umana et al, 2020).…”