T‐bet⁺ memory B cells: Generation, function, and fate

Abstract

Summary B cells expressing the transcription factor T‐bet have emerged as participants in a number of protective and pathogenic immune responses. T‐bet+ B cells characteristically differentiate in response to combined Toll‐like receptor and cytokine signaling, contribute to protective immunity against intracellular pathogens via IgG2a/c production and antibody‐independent mechanisms, and are prone to produce autoantibodies. Despite recent advances, a number of questions remain regarding the basic biology of T‐bet+ B cells and their functional niche within the immune system. Herein, we review the discovery and defining characteristics of the T‐bet+ B cell subset in both mice and humans. We further discuss their origins, the basis for their persistence, and their potential fate in vivo. Evidence indicates that T‐bet+ B cells represent a distinct, germinal center‐derived memory population that may serve as an important therapeutic target for the improvement of humoral immunity and prevention of autoimmunity.

Single cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse immune cell subtypes including T-bet+B cells

“…In humans, T-bet + B cells have been detected in peripheral blood in a variety of chronic inflammatory contexts including systemic lupus erythematosus (64,65), chronic malaria exposure (66,67), and chronic viral infection (16,40,68). Although a universal definition and designated function for these cells remains elusive, T-bet + B cells are often classified as atypical memory B cells and, at least in some contexts, are thought to arise from repetitive BCR stimulation (17). Indeed, human T-bet + B cells are enriched among virus-specific B cells in HIV infection (16).…”

“…In humans, T-bet + B cells have been described as "atypical memory B cells," appearing in the peripheral blood during chronic infection and/or inflammation (17,34). Although specific markers and/or gene expression patterns vary in different datasets, these B cells are often found to express ITGAM (CD11b), ITGAX (CD11c), as well as genes that modulate BCR signaling (including FCRL4, FGR, and HCK) (35)(36)(37)(38)(39).…”

“…Remarkably, we found that a large portion of the horse peripheral B cell compartment is comprised of T-bet + B cells. Cellular analogs of this population in human and mouse are associated with chronic infections (16,17).…”

Decoding inflammation, its causes, genomic responses, and emerging countermeasures

“…These cells’ dysfunction and injury lead to systemic inflammation known as toxic shock syndrome that can be controlled by novel intracellular protein and peptide therapies (see below). In autoimmune inflammation, B cells expressing the transcription factor T‐bet, also known as age‐associated B cells (ABC), participate in response to the ligands for Toll‐like receptors 7 and 9, and cytokines by producing in mice IgG2 a/c directed against intracellular viral pathogens . The T‐bet + memory B cells persist in the spleen and are expanded in patients with autoimmune diseases.…”

“…In autoimmune inflammation, B cells expressing the transcription factor Tbet, also known as age-associated B cells (ABC), participate in response to the ligands for Toll-like receptors 7 and 9, and cytokines by producing in mice IgG2 a/c directed against intracellular viral pathogens. 23 The T-bet + memory B cells persist in the spleen and are expanded in patients with autoimmune diseases.…”