CD11bhigh B Cells Increase after Stroke and Regulate Microglia

Abstract

Recent studies have highlighted the deleterious contributions of B cells to post-stroke recovery and cognitive decline. Different B cell subsets have been proposed on the basis of expression levels of transcription factors (e.g., T-bet) as well as specific surface proteins. CD11b (a-chain of integrin) is expressed by several immune cell types and is involved in regulation of cell motility, phagocytosis, and other essential functions of host immunity. Although B cells express CD11b, the CD11b high subset of B cells has not been well characterized, especially in immune dysregulation seen with aging and after stroke. Here, we investigate the role of CD11b high B cells in immune responses after stroke in young and aged mice. We evaluated the ability of CD11b high B cells to influence pro-and anti-inflammatory phenotypes of young and aged microglia (MG). We hypothesized that CD11b high B cells accumulate in the brain and contribute to neuroinflammation in aging and after stroke. We found that CD11b high B cells are a heterogeneous subpopulation of B cells predominantly present in naive aged mice. Their frequency increases in the brain after stroke in young and aged mice. Importantly, CD11b high B cells regulate MG phenotype and increase MG phagocytosis in both ex vivo and in vivo settings, likely by production of regulatory cytokines (e.g., TNF-a). As both APCs and adaptive immune cells with long-term memory function, B cells are uniquely positioned to regulate acute and chronic phases of the post-stroke immune response, and their influence is subset specific.

A potential mechanism clue to the periodic storm from microglia activation and progressive neuron damage induced by paraquat exposure

“…CD11b/CD18 (Mac‐1, CR3), a multifunctional adhesion and recognition receptor, as β integrins subfamily member, is highly expressed in innate immune cells such as microglia. It plays an important role in the immune response by promoting the recruitment of immune cells and participating in the signal pathway 51 . Research shows that CD11b can recognize lipopolysaccharide and amyloid β protein, α‐Syn, and other PAMPs and DAMPs, which mediate a variety of reactions by transmitting signal molecules downstream 39,52 .…”

“…It plays an important role in the immune response by promoting the recruitment of immune cells and participating in the signal pathway. 51 Research shows that CD11b can recognize lipopolysaccharide and amyloid β protein, α-Syn, and other PAMPs and DAMPs, which mediate a variety of reactions by transmitting signal molecules downstream. 39,52 In recent decades, the axis of PI3K/NOX2 has become heated research on the aspect of immunoregulation.…”

Neutrophil dynamics and inflammaging in acute ischemic stroke: A transcriptomic review

“…Reports on age-related infarct size in the literature are mixed. Many showed that aged mice have significantly smaller infarct sizes ( Liu et al, 2009 ; Manwani et al, 2014 ; Zhao S. et al, 2017 ; Korf et al, 2022 ), while the opposite result has also been recorded ( Shen et al, 2019 ; Liberale et al, 2021 ). Recent data suggests that this difference might be because inflammatory insults that compromise BBB are independent of infarct sizes ( Dénes et al, 2011 ).…”

The central role of peripheral inflammation in ischemic stroke

“…While phagocytosis may be beneficial in clearing necrotic tissue, TNF-a is a notorious pro-inflammatory cytokine. 110 Thus, further research on CD11b high B cells is needed prior to therapeutic development for stroke, especially given the overlap between CD11b high B cells, age, and stroke prognoses. As demonstrated, there are several therapies focused on the regulation of T and B-cell activity, and, given these cells apparent role in stroke pathology, these therapies should be tested in patients with stroke.…”