T-bet-expressing B cells during HIV and HCV infections

Abstract

T-bet-expressing B cells, first identified as perpetuators of autoimmunity, were recently shown to be critical for murine antiviral responses. While their role in human viral infections remains unclear, B cells expressing T-bet or demonstrating a related phenotype have been described in individuals chronically infected with HIV or HCV, suggesting these cells represent a component of human antiviral responses. In this review, we discuss the induction of T-bet in B cells following both HIV and HCV infections, the factors driving T-bet+ B cell expansions, T-bet’s relationship to atypical memory B cells, and the consequences of T-bet induction. We propose potential antiviral roles for T-bet+ B cells and discuss whether this population poses any utility to the HIV and HCV immune responses.

Signals that drive T-bet expression in B cells

“…Whether this solely reflects the effector function of IgG2a/c, or involves other T-bet driven mediators produced by B cells, such as IFN-γ, for full effect remains unclear. In addition to these incisive findings, reports in several different viral infection systems are consistent with a central role for Tbet+ B cells in immune protection [22,29,33,34,36]. In influenza infection, antigen-specific T-bet + B cells can be detected as late as 100 days post infection where they make up about 20–30% of the total antigen-specific B cell pool [28].…”

“…Similarly, viral infections, or nucleic acid-based antigens would elicit a Th1 response, where IFNγ and IL-21 together would promote increased T-bet expression in a TLR-dependent manner, enabling class switching to IgG 2a/c and other T-bet-associated characteristics. Indeed, an increasing body of literature implicates T-bet expressing B cells in a variety of infections, including influenza [30], LCMV [33], HCV [34], and HIV [35][36]. …”

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

“…Within these, further phenotypic and functional categories exist; for example, phenotypically defined T cell subsets differ in anatomic location, cytokine profiles, and the key transcriptional regulators that control these features. [21][22][23][24][25][26] These T-bet + B cells have been identified in both mice and humans in a variety of contexts, including aging, [27][28][29] autoimmunity, 28,[30][31][32][33][34] and infection. Thus, Bmem with distinct phenotypic and functional abilities have been described by several groups, [11][12][13][14][15][16] and PC pools with profoundly different turnover rates are now appreciated.…”

“…[6][7][8][9][10] Analogous broad categories also exist among antigen-experienced cells of the B lineage-memory B cells (Bmem) and antibodysecreting plasma cells (PC)-and reports of subdivisions within these groups have emerged in the last several years. 26,[35][36][37][38][39][40][41] In this article, we first review the discovery and general characteristics of T-bet + memory B Summary B cells expressing the transcription factor T-bet have emerged as participants in a number of protective and pathogenic immune responses. [17][18][19][20] Within this context, a B cell subset expressing the transcription factor T-bet has been the focus of increasing interest in the last several years, reflected by numerous commentaries and dedicated overview volumes.…”

“…Similarly, different mature pre-immune lymphocyte subsets such as transitional (TR), follicular (FO), marginal zone (MZ), and B1 B cells have characteristic anatomic distributions and play distinct roles in primary immune responses. [21][22][23][24][25][26] These T-bet + B cells have been identified in both mice and humans in a variety of contexts, including aging, [27][28][29] autoimmunity, 28,30-34 and infection. Within these, further phenotypic and functional categories exist; for example, phenotypically defined T cell subsets differ in anatomic location, cytokine profiles, and the key transcriptional regulators that control these features.…”