TY - JOUR
T1 - Aging converts innate B1a cells into potent CD8+ T cell inducers
AU - Lee-Chang, Catalina
AU - Bodogai, Monica
AU - Moritoh, Kanako
AU - Chen, Xin
AU - Wersto, Robert
AU - Sen, Ranjan
AU - Young, Howard A.
AU - Croft, Michael
AU - Ferrucci, Luigi
AU - Biragyn, Arya
PY - 2016/4/15
Y1 - 2016/4/15
N2 - B cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL+ MHC class-IHi CD86Hi B cells of unknown origin. In this article, we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. They induce expression and activation of 4-1BBL and IFN-gR1 on B1a cells to subsequently upregulate membrane TNF-α and CD86. As a result, activated B1a/4BL cells induce expression of granzyme B in CD8+ T cells by targeting TNFR2 via membrane TNF-α and providing costimulation with CD86. Thus, for the first time, to our knowledge, these results indicate that aging affects the function of B1a cells. Upon aging, these cells lose their tumor-supporting activity and become inducers of potentially antitumor and autoimmune CD8+ T cells.
AB - B cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL+ MHC class-IHi CD86Hi B cells of unknown origin. In this article, we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. They induce expression and activation of 4-1BBL and IFN-gR1 on B1a cells to subsequently upregulate membrane TNF-α and CD86. As a result, activated B1a/4BL cells induce expression of granzyme B in CD8+ T cells by targeting TNFR2 via membrane TNF-α and providing costimulation with CD86. Thus, for the first time, to our knowledge, these results indicate that aging affects the function of B1a cells. Upon aging, these cells lose their tumor-supporting activity and become inducers of potentially antitumor and autoimmune CD8+ T cells.
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U2 - 10.4049/jimmunol.1502034
DO - 10.4049/jimmunol.1502034
M3 - Article
C2 - 26983789
AN - SCOPUS:84974803177
SN - 0022-1767
VL - 196
SP - 3385
EP - 3397
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -