Antigen‐dependent interactions between regulatory B cells and T cells at the T:B border inhibit subsequent T cell interactions with DCs. Issue 1 (30th August 2019)

• Record Type: Journal Article
• Authors: Mohib, Kanishka; Cherukuri, Aravind; Zhou, Yu; Ding, Qing; Watkins, Simon C.; Rothstein, David M.
• Is Part Of: American journal of transplantation. Volume 20:Issue 1(2020)
• Page Start: 52
• Page End: 63
• Publication Date: 2019-08-30
• Subjects: basic (laboratory) research/science -- immunobiology -- lymphocyte biology -- tolerance: mechanisms; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.15546
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : IL‐10+ regulatory B cells (Bregs) inhibit immune responses in various settings. While Bregs appear to inhibit inflammatory cytokine expression by CD4+ T cells and innate immune cells, their reported impact on CD8+ T cells is contradictory. Moreover, it remains unclear which effects of Bregs are direct versus indirect. Finally, the subanatomical localization of Breg suppressive function and the nature of their intercellular interactions remain unknown. Using novel tamoxifen‐inducible B cell–specific IL‐10 knockout mice, we found that Bregs inhibit CD8+ T cell proliferation and inhibit inflammatory cytokine expression by both CD4+ and CD8+ T cells. Sort‐purified Bregs from IL‐10‐reporter mice were adoptively transferred into wild‐type hosts and examined by live‐cell imaging. Bregs localized to the T:B border, specifically entered the T cell zone, and made more frequent and longer contacts with both CD4+ and CD8+ T cells than did non‐Bregs. These Breg:T cell interactions were antigen‐specific and reduced subsequent T:DC contacts. Thus, Bregs inhibit T cells through direct cognate interactions that subsequently reduce DC:T cell interactions. Abstract : Using IL‐10 reporter mice, the authors find that IL‐10+ Bregs are similarly comprised of plasmablasts, follicular and marginal zone subsets, and in situ visualization reveals that Bregs interact directly with effector T cells in an Ag‐specific manner at the T:B border.