Transient antigen priming promotes B cells recruitment into humoral response or return to quiescence in vivo.

Abstract

Abstract Consistent with the Bretscher and Cohn’s two-signal model of lymphocyte activation, B cells must acquire antigen (Ag) via their B cell receptors (BCR), and then get help from cognate Th cells to initiate long-term antibody responses. Matzinger’s model then implied that for immune tolerance, BCR signaling in the absence of T cell help must lead to B cell anergy or death. This view has been supported by multiple in vivo studies of B cells continuously exposed to self-Ags. However, the fate of B cells transiently exposed to Ag in vivo is unclear. Intravital imaging suggested the transient dynamics of large particulate foreign Ags acquisition by B cells during the initial phase of immune response, but could not address whether such exposure is sufficient for B cell participation in the humoral response. In this study we show that in the presence of T cell help, transient single Ag acquisition promotes B cells’ recruitment into the germinal center, memory and plasma cell responses in vivo. We also demonstrate that transiently Ag-primed B cells do not undergo apoptosis in the absence of T cell help in vivo, but return to quiescence, and upon reacquisition of Ag and T cell help can mount a potent humoral response. Based on these findings we suggest a possibility of multiple cycles of Ag acquisition by B cells and return to quiescence. When T cell help is limiting, this mechanism may promote a greater diversity of B cell clones to enter the humoral response to foreign Ags. However, a failure of B cells to undergo anergy or apoptosis after a transient acquisition of self-Ags may contribute to breach of B cell tolerance.